What are the recommended antibiotics for treating Pseudomonas infections?

Antibiotic Treatment for Pseudomonas Infections

For susceptible Pseudomonas aeruginosa infections, use piperacillin-tazobactam 3.375-4.5g IV every 6 hours as first-line monotherapy, or alternatively ceftazidime 2g IV every 8 hours, cefepime 2g IV every 8-12 hours, or meropenem 1g IV every 8 hours. 1, 2

First-Line Antibiotic Selection

Standard Susceptible Strains

For non-severe infections with susceptible P. aeruginosa, monotherapy with an antipseudomonal β-lactam is preferred and equally effective as combination therapy with fewer adverse events 1:

• Piperacillin-tazobactam: 3.375-4.5g IV every 6 hours (preferred first-line agent) 1, 3
• Ceftazidime: 2g IV every 8 hours 1, 2, 3
• Cefepime: 2g IV every 8-12 hours 1, 2
• Meropenem: 1g IV every 8 hours 1, 2

Extended-infusion piperacillin-tazobactam (3.375g IV over 4 hours every 8 hours) demonstrates superior outcomes in critically ill patients, with significantly lower 14-day mortality (12.2% vs 31.6%) and shorter hospital stays (21 vs 38 days) compared to standard intermittent infusions 4.

Fluoroquinolone Options

• Ciprofloxacin: 400mg IV every 8 hours or 750mg PO twice daily (high-dose regimen for Pseudomonas) 1, 2, 5, 6
• Ciprofloxacin is the only reliable oral option for Pseudomonas infections and achieves sputum concentrations 46-90% of serum levels 7, 5
• Levofloxacin has antipseudomonal activity but is generally less potent than ciprofloxacin 1

Combination Therapy Indications

Add a second antipseudomonal agent (aminoglycoside or fluoroquinolone) for: 7, 1, 2

• Critically ill patients (ICU admission, septic shock, ARDS) 7, 1
• Severe infections including ventilator-associated pneumonia or nosocomial pneumonia 7, 1
• Suspected or documented multidrug-resistant strains 1
• Prior antibiotic use within 90 days 1
• Local resistance rates exceeding 10-20% 1

Recommended Combinations

For severe Pseudomonas infections, use an antipseudomonal β-lactam PLUS one of the following: 7, 1, 2

• Aminoglycoside (tobramycin preferred over gentamicin due to lower nephrotoxicity): Initial dose ~10 mg/kg/day IV, with once-daily dosing equally efficacious and less toxic than three-times-daily dosing 7, 2

  • Target peak levels: 25-35 mg/mL 2
  • Monitor renal function and auditory function to minimize nephrotoxicity and ototoxicity 2

• Ciprofloxacin: 400mg IV every 8 hours or levofloxacin 750mg IV daily 7, 1

Never use aminoglycoside monotherapy for empirical coverage or bacteremia due to rapid resistance emergence 1. Aminoglycosides should only be considered as monotherapy for uncomplicated urinary tract infections 1.

Difficult-to-Treat Resistant (DTR) Pseudomonas

For multidrug-resistant strains, newer agents are preferred first-line options 1, 2:

• Ceftolozane/tazobactam: 1.5-3g IV every 8 hours 1, 2
• Ceftazidime/avibactam: 2.5g IV every 8 hours 1, 2
• Imipenem/cilastatin/relebactam: 1.25g IV every 6 hours 1
• Cefiderocol: For metallo-β-lactamase producers (70.8% clinical cure rate) 2
• Colistin: 5mg CBA/kg IV loading dose, then 2.5mg CBA maintenance (reserved for extensively resistant strains) 1, 2

Site-Specific Considerations

Community-Acquired Pneumonia with Pseudomonas Risk

Use antipseudomonal β-lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) PLUS either ciprofloxacin/levofloxacin 750mg OR aminoglycoside PLUS azithromycin to cover atypical pathogens 7, 2.

Risk factors requiring Pseudomonas coverage include: 7

• Structural lung disease (bronchiectasis)
• Severe COPD with frequent exacerbations requiring steroids/antibiotics
• Prior antibiotic therapy
• Gram-negative rods on Gram stain of respiratory specimens

Urinary Tract Infections

• Uncomplicated/mild: Ciprofloxacin 750mg PO twice daily 5
• Complicated/severe: Piperacillin-tazobactam IV or ceftazidime/cefepime IV 5
• Resistant strains: Carbapenems (imipenem, meropenem) or colistin 5

Cystic Fibrosis Patients

• Acute exacerbations: High-dose IV β-lactam (ceftazidime 150-250 mg/kg/day divided in 3-4 doses, maximum 12g daily) PLUS aminoglycoside 7, 2
• Maintenance therapy: Inhaled tobramycin 300mg twice daily or colistin 1-2 million units twice daily 7, 2
• Early colonization eradication: Aggressive systemic antibiotic plus inhaled antibiotic to delay chronic infection 2
• Always base selection on susceptibility testing due to higher resistance rates 2, 5

Treatment Duration

• Standard infections: 7-10 days 1
• Pneumonia or bloodstream infections: 10-14 days 1, 2
• Complicated infections or immunocompromised hosts: 10-14 days or longer 2, 5
• Nosocomial/ventilator-associated pneumonia: 7-14 days 2

Critical Pitfalls to Avoid

• Do not use ceftazidime as empirical monotherapy due to poor gram-positive coverage and increasing resistance 1
• Do not use ertapenem for Pseudomonas coverage—it lacks antipseudomonal activity 1, 2
• Do not use ampicillin/sulbactam—it has no clinically relevant activity against P. aeruginosa 2
• Avoid imipenem/cilastatin in CF patients due to higher rates of allergic reactions 2
• Do not underdose—use maximum recommended doses to prevent treatment failure and resistance development 7, 1, 2
• Always check local antibiograms when available to guide empiric therapy 1
• Adjust therapy based on susceptibility results—de-escalate to monotherapy once susceptibilities are known if organism is susceptible 2

Special Dosing Considerations

For cystic fibrosis patients, higher doses are required due to altered pharmacokinetics 7, 2:

• Ceftazidime: 150-250 mg/kg/day (maximum 12g daily)
• Meropenem: 60-120 mg/kg/day (maximum 6g daily), can escalate to 3 × 2g in 3-hour infusions for severe cases
• Tobramycin: ~10 mg/kg/day IV with once-daily dosing preferred