What antibiotics are effective against Pseudomonas (Pseudomonas aeruginosa) infections?

Antibiotics Effective Against Pseudomonas aeruginosa

First-Line Antipseudomonal β-Lactams

For most Pseudomonas aeruginosa infections, start with an antipseudomonal β-lactam as monotherapy unless the patient is critically ill or has risk factors for multidrug resistance. 1, 2

The preferred first-line agents include:

• Piperacillin-tazobactam 3.375-4.5g IV every 6 hours is the most commonly recommended initial agent, with FDA approval for nosocomial pneumonia caused by P. aeruginosa (must be combined with an aminoglycoside for this indication) 3, 1
• Ceftazidime 2g IV every 8 hours provides reliable antipseudomonal coverage and achieves therapeutic concentrations in most body tissues 4, 1, 2
• Cefepime 2g IV every 8-12 hours offers broad-spectrum coverage including P. aeruginosa with lower neurotoxicity risk compared to some alternatives 1, 2
• Meropenem 1g IV every 8 hours (can escalate to 2g every 8 hours for severe infections) is the preferred carbapenem for P. aeruginosa, offering higher maximum dosing than imipenem 1, 2

Critical distinction: Not all broad-spectrum antibiotics cover Pseudomonas. Ceftriaxone, cefazolin, ampicillin-sulbactam, and ertapenem completely lack antipseudomonal activity despite being broad-spectrum agents 1, 2

When to Add Combination Therapy

Add a second antipseudomonal agent from a different drug class in these specific scenarios: 5, 1, 2

• ICU admission or septic shock 5, 1, 2
• Ventilator-associated or nosocomial pneumonia 5, 1, 3
• Structural lung disease (bronchiectasis, cystic fibrosis) 5, 1
• Prior IV antibiotic use within 90 days 1, 2
• Documented Pseudomonas on Gram stain 1, 2
• High local prevalence (>10-20%) of multidrug-resistant strains 1, 2

For combination therapy, pair your β-lactam with either: 5, 1, 2

• Tobramycin 5-7 mg/kg IV once daily (preferred aminoglycoside due to lower nephrotoxicity than gentamicin, with target peak levels of 25-35 mg/mL) 1, 6
• Amikacin 15-20 mg/kg IV once daily (alternative aminoglycoside) 1, 2
• Ciprofloxacin 400mg IV every 8 hours (fluoroquinolone option with excellent antipseudomonal activity) 1, 2

The FDA label for piperacillin-tazobactam explicitly states that "nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside" at a dose of 4.5g every 6 hours 3

Oral Therapy Options

Ciprofloxacin 750mg PO twice daily is the ONLY reliable oral antibiotic for Pseudomonas coverage. 1, 2 This high-dose regimen is essential because:

• Oral bioavailability matches IV levels (allowing reliable oral therapy) 1
• Achieves sputum concentrations of 46-90% of serum levels 1
• Standard 500mg dosing is insufficient for Pseudomonas infections 1

Levofloxacin 750mg PO daily can serve as a second-line oral option but has weaker antipseudomonal activity than ciprofloxacin 1, 2

Oral therapy is appropriate for: 1

• Mild to moderate infections in clinically stable patients
• COPD exacerbations with Pseudomonas risk factors in non-severely ill patients
• Step-down therapy after clinical improvement on IV antibiotics (switch by day 3 if stable)

Treatment Duration

Standard duration is 7-14 days depending on infection site and severity: 1, 2

• 7-10 days for most infections including uncomplicated cases 2, 3
• 10-14 days for P. aeruginosa pneumonia or bloodstream infections 2
• 14 days for documented respiratory Pseudomonas infections, particularly in bronchiectasis 1
• 7-14 days for nosocomial/ventilator-associated pneumonia 5, 1, 3

Newer Agents for Difficult-to-Treat Resistant Strains

For multidrug-resistant P. aeruginosa (DTR-PA), escalate to newer β-lactam combinations: 1, 2, 7

• Ceftolozane-tazobactam 1.5-3g IV every 8 hours (preferred for pneumonia) 1, 2, 7
• Ceftazidime-avibactam 2.5g IV every 8 hours (equally effective for non-respiratory infections) 1, 2, 7
• Imipenem-cilastatin-relebactam 1.25g IV every 6 hours (retains activity when resistance develops to above agents) 1, 2
• Cefiderocol (specifically for metallo-β-lactamase producers, with 70.8% clinical cure rates) 1, 7

Inhaled Antibiotics for Chronic Respiratory Infections

For cystic fibrosis patients or chronic bronchiectasis with P. aeruginosa colonization, add maintenance inhaled therapy: 5, 1

• Tobramycin 300mg inhaled twice daily (month on/month off regimen shown superior to standard care) 5, 1
• Colistin 1-2 million units inhaled twice daily (alternative for maintenance therapy) 5, 1

These reduce exacerbations and maintain lung function between IV courses 5, 1

Critical Dosing Considerations

Use extended or continuous infusions for critically ill patients with severe P. aeruginosa infections: 1

• Piperacillin-tazobactam as a 4-hour infusion (rather than 30-minute bolus) reduces 14-day mortality in patients with APACHE II ≥17 1
• Extended infusions maximize time above MIC and improve clinical outcomes 1

Higher doses are required for cystic fibrosis patients due to altered pharmacokinetics: 1

• Ceftazidime 150-250 mg/kg/day divided in 3-4 doses (maximum 12g daily) 1
• Meropenem 60-120 mg/kg/day divided in 3 doses (maximum 6g daily, can escalate to 3 × 2g in severe cases) 1

Common Pitfalls to Avoid

Never use these antibiotics for Pseudomonas coverage despite being "broad-spectrum": 1, 2

• Ceftriaxone (no antipseudomonal activity) 1
• Ertapenem (explicitly lacks P. aeruginosa coverage) 1, 2
• Ampicillin-sulbactam (no clinically relevant activity) 1
• Vancomycin (only covers Gram-positives, zero activity against Pseudomonas) 2

Avoid underdosing—use maximum recommended doses for severe infections: 1

• Standard doses may be inadequate for P. aeruginosa
• Underdosing leads to treatment failure and resistance development

Never extend oral ciprofloxacin monotherapy beyond 14 days: 1

• Promotes resistance without proven benefit
• Residual sputum in bronchiectasis does not justify extension
• If failing at 14 days, re-evaluate and obtain new cultures rather than continuing same antibiotic

Aminoglycoside monotherapy should NEVER be used for bacteremia or empirical coverage: 2

• Rapid resistance emergence makes this dangerous
• Only acceptable for uncomplicated urinary tract infections

Gentamicin is NOT the preferred aminoglycoside for P. aeruginosa: 1

• Tobramycin has lower nephrotoxicity and ototoxicity
• Gentamicin should only be used when tobramycin is unavailable

Monitoring Requirements

For aminoglycoside therapy, mandatory monitoring includes: 1

• Drug levels (target tobramycin peak 25-35 mg/mL)
• Renal function (creatinine, BUN)
• Auditory function (baseline and periodic audiometry)

For fluoroquinolone therapy: 1

• Monitor QTc interval, especially if baseline >500ms or concurrent QT-prolonging drugs
• Assess clinical response daily

Obtain sputum culture before starting antibiotics to confirm susceptibility and guide therapy. 1 Consider switching to IV combination therapy if no clinical improvement by day 3-5 1

De-escalation Strategy

Once susceptibility results are available and the patient is improving, narrow to monotherapy if the organism is susceptible. 1, 2 This carbapenem-sparing and antibiotic stewardship approach prevents unnecessary broad-spectrum exposure while maintaining efficacy 1, 2