Antibiotic Management for Hospital-Acquired Pneumonia
For patients with HAP, empiric antibiotic selection must be stratified by mortality risk and MDR pathogen risk factors, with broad-spectrum antipseudomonal beta-lactams forming the backbone of therapy, combined with MRSA coverage when indicated. 1
Risk Stratification Framework
Low-risk patients (no high mortality risk, no MDR risk factors) should receive monotherapy with one of the following 1:
- Piperacillin-tazobactam 4.5g IV q6h
- Cefepime 2g IV q8h
- Levofloxacin 750mg IV daily
- Imipenem 500mg IV q6h
- Meropenem 1g IV q8h
High-risk patients require dual antipseudomonal coverage plus MRSA coverage. High-risk criteria include 1, 2:
- Septic shock or need for ventilatory support due to HAP
- Prior IV antibiotic use within 90 days
- Hospitalization >5 days
- Structural lung disease (bronchiectasis, cystic fibrosis)
- Treatment in a unit where MRSA prevalence is >20% or unknown
Empiric Regimens for High-Risk HAP
For high-risk patients, use TWO antipseudomonal agents from different classes (avoid combining two beta-lactams) plus MRSA coverage 1, 2:
Dual antipseudomonal options (choose one beta-lactam PLUS one aminoglycoside or fluoroquinolone) 1:
- Piperacillin-tazobactam 4.5g IV q6h OR cefepime/ceftazidime 2g IV q8h OR meropenem 1g IV q8h
- PLUS amikacin 15-20 mg/kg IV daily OR gentamicin 5-7 mg/kg IV daily OR tobramycin 5-7 mg/kg IV daily
- OR ciprofloxacin 400mg IV q8h OR levofloxacin 750mg IV daily
MRSA coverage (add one of the following) 1:
- Vancomycin 15 mg/kg IV q8-12h (target trough 15-20 mg/mL; consider loading dose 25-30 mg/kg for severe illness)
- OR linezolid 600mg IV q12h
Critical Decision Points for MRSA Coverage
Include empiric MRSA coverage if ANY of the following are present 1, 2:
- Prior IV antibiotic use within 90 days
- Unit MRSA prevalence >20% or unknown
- Prior MRSA colonization/infection
- Septic shock or ventilatory support requirement
Omit MRSA coverage only if the patient has none of these risk factors AND ensure the regimen includes MSSA coverage (piperacillin-tazobactam, cefepime, levofloxacin, imipenem, or meropenem all provide adequate MSSA coverage) 1.
Definitive Therapy Based on Culture Results
For Pseudomonas aeruginosa
Base definitive therapy on antimicrobial susceptibility testing 1:
- Patients NOT in septic shock or high mortality risk: Use monotherapy with a susceptible agent 1
- Patients IN septic shock or high mortality risk (>25% mortality): Continue combination therapy with two susceptible agents 1
- Never use aminoglycoside monotherapy for Pseudomonas 1
Once septic shock resolves, de-escalate to monotherapy 1.
For MRSA
Switch to vancomycin or linezolid for proven MRSA 1. These are superior to alternative agents for HAP due to MRSA.
For Methicillin-Susceptible Staphylococcus aureus (MSSA)
De-escalate immediately to nafcillin, oxacillin, or cefazolin once MSSA is confirmed 3, 4. These agents are superior to broad-spectrum antibiotics like piperacillin-tazobactam or vancomycin for proven MSSA 3, 4. Continuing broad-spectrum therapy after MSSA identification increases resistance risk and C. difficile without improving outcomes 3.
For ESBL-Producing Gram-Negatives
Base antibiotic selection on susceptibility testing and patient-specific factors (allergies, comorbidities) 1.
For Acinetobacter Species
If susceptible: Use carbapenem or ampicillin/sulbactam 1
If only polymyxin-susceptible: Use IV polymyxin (colistin or polymyxin B) plus adjunctive inhaled colistin 1
Avoid tigecycline for Acinetobacter HAP 1
For Carbapenem-Resistant Pathogens
Use IV polymyxins (colistin or polymyxin B) plus adjunctive inhaled colistin 1.
Duration of Therapy
Treat for 7 days in uncomplicated cases with good clinical response 2. Extend to 14 days for complicated infections or inadequate initial response 5, 2.
De-escalation Strategy
De-escalate by day 3 based on culture results and clinical response 2:
- Narrow from dual to single antipseudomonal agent once susceptibilities known (if not in septic shock) 1
- Switch from vancomycin/linezolid to nafcillin/oxacillin/cefazolin for MSSA 3, 4
- Discontinue MRSA coverage if cultures negative for MRSA 1
Common Pitfalls to Avoid
Never use aminoglycoside monotherapy for Pseudomonas—it leads to rapid resistance and treatment failure 1, 6.
Do not continue broad-spectrum empiric antibiotics once a specific pathogen is identified—this increases resistance without improving outcomes 3, 7.
Do not omit dual antipseudomonal coverage in patients with prior IV antibiotics within 90 days, structural lung disease, or high mortality risk 1, 2, 6.
Do not use vancomycin for proven MSSA—beta-lactams (nafcillin, oxacillin, cefazolin) are superior 3, 4.
Avoid monotherapy for Pseudomonas in critically ill patients—combination therapy reduces resistance emergence and improves outcomes in septic shock 1, 6.