What are the recommended antibiotic (abx) regimens for Pseudomonas coverage?

Pseudomonas Antibiotic Coverage

For empiric Pseudomonas coverage, use an antipseudomonal β-lactam as monotherapy for non-critically ill patients, but add a second agent from a different class (aminoglycoside or fluoroquinolone) for critically ill patients, severe infections, or those with risk factors for multidrug resistance. 1

First-Line Antipseudomonal β-Lactams

The preferred initial agents include:

• Piperacillin-tazobactam 4.5g IV every 6 hours (most commonly recommended first-line agent) 1, 2
• Cefepime 2g IV every 8 hours 1, 3
• Ceftazidime 2g IV every 8 hours 1, 3
• Meropenem 1g IV every 8 hours 1, 3
• Imipenem/cilastatin 1g IV every 8 hours 1

Extended infusions of piperacillin-tazobactam (3.375-4.5g infused over 4 hours every 8 hours) significantly improve outcomes compared to standard 30-minute infusions, particularly in critically ill patients, reducing 14-day mortality from 31.6% to 12.2% 4, 5

When to Add Combination Therapy

Add a second antipseudomonal agent in these situations:

• Critically ill patients or septic shock 1
• Ventilator-associated or nosocomial pneumonia 1, 6
• Prior IV antibiotic use within 90 days 1, 2
• Structural lung disease (bronchiectasis, cystic fibrosis) 1
• Local resistance rates >10-20% 2
• Documented Pseudomonas on Gram stain 1

Second Agent Options for Combination Therapy

Choose ONE of the following to combine with your β-lactam:

Aminoglycosides (preferred for severe infections):

• Tobramycin 5-7 mg/kg IV daily (preferred over gentamicin due to lower nephrotoxicity) 1, 3
• Amikacin 15-20 mg/kg IV daily 1
• Requires therapeutic drug monitoring with target tobramycin peak levels of 25-35 mg/mL 3

Fluoroquinolones:

• Ciprofloxacin 400mg IV every 8 hours 1, 3
• Levofloxacin 750mg IV daily (less potent than ciprofloxacin for Pseudomonas) 1, 6

The combination of piperacillin-tazobactam plus amikacin demonstrates the highest synergy rates (42%) compared to fluoroquinolone combinations 7

Oral Options

Ciprofloxacin 750mg PO twice daily is the only reliable oral agent for Pseudomonas, achieving sputum concentrations 46-90% of serum levels 8, 2. However, oral monotherapy is insufficient for severe infections including pneumonia, bacteremia, or osteomyelitis 8

Multidrug-Resistant Pseudomonas

For difficult-to-treat resistant strains, use:

• Ceftolozane-tazobactam 1.5-3g IV every 8 hours (first-line for MDR non-metallo-β-lactamase producers) 1, 3, 2
• Ceftazidime-avibactam 2.5g IV every 8 hours 1, 3, 2
• Cefiderocol for metallo-β-lactamase producers (70.8% clinical cure rate) 3

Critical Pitfalls to Avoid

• Never use aminoglycoside monotherapy for empiric coverage or bacteremia due to rapid resistance emergence 2
• Avoid ertapenem - it completely lacks antipseudomonal activity despite being a carbapenem 3, 2
• Do not use ceftriaxone or cefazolin - these non-antipseudomonal cephalosporins have no Pseudomonas coverage 1
• Avoid ampicillin-sulbactam - no clinically relevant activity against Pseudomonas 3
• Levofloxacin is inferior to ciprofloxacin for Pseudomonas and should only be used when ciprofloxacin is unavailable 2, 6
• For documented Pseudomonas pneumonia, combination therapy with an anti-pseudomonal β-lactam is mandatory even when using levofloxacin 6

Treatment Duration

• 7-10 days for most infections 2
• 10-14 days for pneumonia or bloodstream infections 2
• 7-14 days for nosocomial/ventilator-associated pneumonia 1, 3

Special Considerations

For patients with severe penicillin allergy, aztreonam 2g IV every 8 hours is the only monobactam with antipseudomonal activity and can be safely used 1, 2

For cystic fibrosis patients, higher doses are required: ceftazidime 150-250 mg/kg/day or meropenem 60-120 mg/kg/day due to altered pharmacokinetics 3, 2