What empiric antibiotic regimen is recommended for hospital-acquired pneumonia (HAP) in a patient with a history of Pseudomonas infection treated with cefepime (Cefepime), who now presents with worsening left lower lobe consolidation on chest X-ray (CXR) and leukocytosis?

Empiric Antibiotic Regimen for HAP with Prior Pseudomonas and Recent Cefepime Exposure

Given this patient's recent Pseudomonas infection treated with cefepime within the last month, worsening clinical picture, and high risk for multidrug-resistant organisms, you should use dual antipseudomonal coverage with an antipseudomonal beta-lactam from a different class (piperacillin-tazobactam, ceftazidime, or a carbapenem) PLUS either an aminoglycoside or fluoroquinolone, combined with vancomycin or linezolid for MRSA coverage. 1

Risk Stratification

This patient has multiple high-risk features mandating broad-spectrum empiric therapy:

• Prior IV antibiotic use within 90 days (cefepime last month) - this is a critical risk factor for both MDR gram-negatives and MRSA 1, 2
• Tracheostomy - represents structural airway alteration increasing risk for gram-negative pathogens 1
• Clinical deterioration with worsening infiltrate and leukocytosis despite recent treatment 2
• Prior Pseudomonas colonization/infection - significantly increases risk of recurrent resistant Pseudomonas 1, 3

Recommended Empiric Regimen

Dual Antipseudomonal Coverage (Choose ONE combination):

Option 1 (Preferred):

• Piperacillin-tazobactam 4.5g IV every 6 hours (extended infusion over 4 hours if possible) PLUS tobramycin or amikacin (dosed by pharmacy protocol) 1, 2

Option 2:

• Ceftazidime 2g IV every 8 hours PLUS ciprofloxacin 400mg IV every 8 hours 1, 4, 3

Option 3:

• Meropenem 1-2g IV every 8 hours PLUS tobramycin or amikacin 1, 3

PLUS MRSA Coverage:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (target trough 15-20 mcg/mL) OR linezolid 600mg IV every 12 hours 1, 2

Rationale for Dual Antipseudomonal Therapy

You must use two different antibiotic classes against Pseudomonas because:

• Prior IV antibiotic use within 90 days is an explicit indication for dual coverage per IDSA/ATS guidelines 1
• Tracheostomy represents structural lung disease, another indication for dual therapy 1
• Clinical failure/worsening suggests potential resistance to prior cefepime 1, 2
• Monotherapy for pseudomonal HAP leads to rapid resistance development and high clinical failure rates 3
• Aminoglycosides should never be used as the sole antipseudomonal agent 1

Why Avoid Cefepime

Do not use cefepime again - the patient was just treated with this agent last month for Pseudomonas, and now presents with clinical worsening. This suggests either:

• Persistent/recurrent infection with potentially cefepime-resistant Pseudomonas
• New infection with a different resistant organism
• Selection pressure from recent cefepime use 5, 3

MRSA Coverage Justification

MRSA coverage is mandatory because:

• Prior IV antibiotic use within 90 days is an explicit indication 1, 2
• If your unit's MRSA prevalence among S. aureus isolates is >20% or unknown, this mandates MRSA coverage 1
• Tracheostomy patients have increased MRSA risk 2

De-escalation Strategy

Once sputum cultures return (typically 48-72 hours):

• If Pseudomonas susceptible to single agent: Narrow to monotherapy with the most appropriate agent based on susceptibilities 1, 2
• If MSSA (not MRSA) identified: Switch vancomycin/linezolid to nafcillin, oxacillin, or cefazolin, OR continue piperacillin-tazobactam if already using it 6, 7
• If MRSA ruled out: Discontinue vancomycin/linezolid 7, 2
• If no Pseudomonas and only susceptible gram-negatives: Narrow to appropriate single agent 2

Critical Pitfalls to Avoid

• Do not use monotherapy in this high-risk patient - this is associated with treatment failure and resistance emergence 1, 3
• Do not repeat cefepime given recent exposure and clinical worsening 5
• Do not omit MRSA coverage given prior antibiotic exposure 1, 2
• Do not use aminoglycoside alone for Pseudomonas - must be combined with beta-lactam 1
• Reassess by day 3 - failure to de-escalate based on cultures contributes to resistance and C. difficile risk 2