What are the recommended treatments for Pseudomonas aeruginosa infections?

Antipseudomonal Antibiotic Treatment

For severe Pseudomonas aeruginosa infections, use combination therapy with an antipseudomonal β-lactam (piperacillin-tazobactam, ceftazidime, cefepime, or meropenem) PLUS either an aminoglycoside (tobramycin preferred) or ciprofloxacin to prevent treatment failure and reduce resistance development. 1

First-Line Antipseudomonal β-Lactams

Intravenous Options:

• Piperacillin-tazobactam: 3.375-4.5g IV every 6 hours for standard infections; 4.5g IV every 6 hours for nosocomial pneumonia 2
• Ceftazidime: 150-250 mg/kg/day divided in 3-4 doses (maximum 12g daily) or 2g IV every 8 hours 1, 3
• Cefepime: 100-150 mg/kg/day divided in 2-3 doses (maximum 6g daily) or 2g IV every 8-12 hours 1
• Meropenem: 60-120 mg/kg/day divided in 3 doses (maximum 6g daily) or 1g IV every 8 hours 1

Critical distinction: Avoid imipenem/cilastatin due to higher rates of allergic reactions in Pseudomonas-infected patients 1. Ertapenem has NO activity against Pseudomonas and should never be used 1.

Second Agent Selection for Combination Therapy

Aminoglycoside (Preferred for Severe Infections):

• Tobramycin: ~10 mg/kg/day IV with target peak levels of 25-35 mg/mL 1
• Once-daily dosing is equally efficacious and less toxic than three-times-daily dosing 1
• Tobramycin is preferred over gentamicin due to lower nephrotoxicity 1
• Mandatory monitoring: Aminoglycoside levels, renal function, and auditory function 1

Fluoroquinolone Alternative:

• Ciprofloxacin: 400 mg IV every 8-12 hours OR 750 mg orally every 12 hours 1, 4, 3
• High-dose oral ciprofloxacin (750 mg twice daily) provides adequate serum and bronchial concentrations for Pseudomonas 4

When to Use Combination vs. Monotherapy

Combination therapy is REQUIRED for: 1

• Severe infections or sepsis
• Nosocomial/ventilator-associated pneumonia
• High-risk patients (immunocompromised, neutropenic)
• Critically ill patients

Monotherapy may be acceptable for: 4

• Mild-to-moderate infections in immunocompetent patients
• Confirmed ciprofloxacin susceptibility with oral therapy
• Non-severe urinary tract infections

Site-Specific Treatment Approaches

Nosocomial Pneumonia:

• Piperacillin-tazobactam 4.5g IV every 6 hours PLUS tobramycin for 7-14 days 2
• Continue aminoglycoside if P. aeruginosa is isolated from cultures 2

Urinary Tract Infections:

• First-line oral: Ciprofloxacin 750 mg twice daily 5
• First-line IV: Piperacillin-tazobactam 3.375g every 6 hours 5
• Alternative IV: Ceftazidime or cefepime 5

Respiratory Infections (Non-CF):

• Antipseudomonal β-lactam PLUS aminoglycoside or ciprofloxacin for 10-14 days 1, 4

Cystic Fibrosis Patients:

• Oral: Ciprofloxacin 30 mg/kg/day divided twice daily (maximum 2-3 g/day) 5
• Inhaled maintenance: Tobramycin 300mg twice daily OR colistin 1-2 million units twice daily 1
• Always base selection on susceptibility testing due to higher resistance rates 5

Treatment Duration

• Standard infections: 7-14 days depending on site and severity 1
• Nosocomial pneumonia: 7-14 days 2
• Osteomyelitis: 6 weeks 4
• Immunocompromised hosts: Longer courses may be required 1

Pediatric Dosing

Piperacillin-tazobactam: 2

• 2-9 months: 90 mg/kg (80 mg piperacillin/10 mg tazobactam) every 8 hours for appendicitis/peritonitis; every 6 hours for nosocomial pneumonia

• 9 months: 112.5 mg/kg (100 mg piperacillin/12.5 mg tazobactam) every 8 hours for appendicitis/peritonitis; every 6 hours for nosocomial pneumonia

• 40 kg: Use adult dosing

Ciprofloxacin: 4

• 10-20 mg/kg/dose orally every 12 hours (maximum 750 mg/dose)
• 10 mg/kg/dose IV every 8-12 hours (maximum 400 mg/dose)
• Reserve for infections where benefit outweighs risk; consider pediatric infectious disease consultation 4

Renal Dose Adjustments

For creatinine clearance ≤40 mL/min: 2

• CrCl 20-40: Reduce to 2.25g every 6 hours (3.375g every 6 hours for nosocomial pneumonia)
• CrCl <20: Reduce to 2.25g every 8 hours (2.25g every 6 hours for nosocomial pneumonia)
• Hemodialysis: 2.25g every 12 hours PLUS 0.75g after each dialysis session

Emerging Resistance and Novel Agents

For difficult-to-treat resistant strains: 1

• Ceftolozane-tazobactam and ceftazidime-avibactam are first-line options for resistant Pseudomonas
• Cefiderocol for metallo-β-lactamase producers (70.8% clinical cure rate)
• Colistin 1-2 million units twice daily for multidrug-resistant strains (inhaled or IV)

Critical Pitfalls to Avoid

• Underestimating resistance potential: Never use monotherapy for severe infections—resistance develops rapidly 1, 5
• Inadequate dosing: Use maximum recommended doses to avoid treatment failure and resistance development 1, 5
• Ignoring local resistance patterns: Always check institutional antibiograms before selecting empiric therapy 1, 5
• Forgetting aminoglycoside monitoring: Failure to monitor levels leads to nephrotoxicity and ototoxicity 1
• Using wrong carbapenem: Ertapenem has ZERO activity against Pseudomonas 1
• Prolonged ciprofloxacin monotherapy: Rapid emergence of resistance is a major concern, especially in CF patients 6

Monitoring Requirements

• Clinical response assessment: Within 72 hours of initiating therapy 4
• Aminoglycoside levels: Peak and trough monitoring mandatory 1
• Renal function: Monitor creatinine, especially with aminoglycosides 1
• Auditory function: Baseline and periodic audiometry with aminoglycosides 1
• Follow-up cultures: After completion of therapy to confirm eradication 4
• Susceptibility patterns: Regular monitoring with long-term therapy 1