Recommended Medications for Pseudomonas Infections
For most Pseudomonas aeruginosa infections, start with an antipseudomonal β-lactam as monotherapy (piperacillin-tazobactam, ceftazidime, cefepime, or meropenem), but add a second agent (aminoglycoside or ciprofloxacin) for severe infections, ICU patients, ventilator-associated pneumonia, or when multidrug resistance is suspected. 1
First-Line Antipseudomonal β-Lactams
The following agents are your primary options for susceptible Pseudomonas:
- Piperacillin-tazobactam: 3.375-4.5g IV every 6 hours 1, 2
- Ceftazidime: 2g IV every 8 hours (or 150-250 mg/kg/day divided in 3-4 doses, maximum 12g daily for severe infections) 1, 3
- Cefepime: 2g IV every 8-12 hours (or 50 mg/kg/dose every 8 hours for Pseudomonas infections, maximum 2000 mg/dose) 1, 3
- Meropenem: 1g IV every 8 hours (or 60-120 mg/kg/day divided in 3 doses, maximum 6g daily; can escalate to 2g every 8 hours as 3-hour infusions for severe cases) 1, 3
Critical caveat: Never assume a β-lactam covers Pseudomonas—ceftriaxone, cefazolin, ampicillin/sulbactam, and ertapenem have NO antipseudomonal activity despite being broad-spectrum agents. 1, 2
When to Add Combination Therapy
Add a second antipseudomonal agent from a different class in these specific scenarios:
- ICU admission or critically ill/septic shock patients 1, 2
- Ventilator-associated or nosocomial pneumonia 3, 1
- Structural lung disease (bronchiectasis, cystic fibrosis) 3, 1
- Prior IV antibiotic use within 90 days 1, 2
- Documented Pseudomonas on Gram stain 3, 1
- High local prevalence of multidrug-resistant strains (>10-20% resistance rates) 1, 2
The rationale: Combination therapy prevents inadequate initial therapy and delays resistance development compared to monotherapy, which is critical in severe infections where treatment failure carries high mortality. 3, 1
Second Agent Options for Combination Therapy
When combination therapy is indicated, add ONE of the following:
Aminoglycosides (Preferred for Severe Infections)
- Tobramycin: 5-7 mg/kg IV once daily (preferred over gentamicin due to lower nephrotoxicity; target peak 25-35 mg/mL) 1, 2
- Amikacin: 15-20 mg/kg IV once daily 1, 2
Once-daily aminoglycoside dosing is equally efficacious and less toxic than three-times-daily dosing. 1 Monitor aminoglycoside levels, renal function, and auditory function to minimize nephrotoxicity and ototoxicity. 1
Fluoroquinolones
- Ciprofloxacin: 400mg IV every 8 hours (or 750mg PO twice daily for high-dose oral regimen) 1, 2
- Levofloxacin: 750mg IV/PO daily (less potent than ciprofloxacin for Pseudomonas) 1, 2
Important distinction: Ciprofloxacin is the only fluoroquinolone with reliable antipseudomonal activity; levofloxacin has weaker activity and should be considered second-line. 1 The FDA label confirms levofloxacin requires combination therapy with ceftazidime or piperacillin/tazobactam when Pseudomonas is documented. 4
Site-Specific Considerations
Nosocomial/Ventilator-Associated Pneumonia
Use piperacillin-tazobactam 4.5g IV every 6 hours PLUS tobramycin or ciprofloxacin for 7-14 days. 3, 1 The FDA label explicitly states that where Pseudomonas is documented or presumptive, combination therapy with an anti-pseudomonal β-lactam is recommended. 4
Community-Acquired Pneumonia with Pseudomonas Risk
Use antipseudomonal β-lactam PLUS (ciprofloxacin OR aminoglycoside) PLUS azithromycin to cover atypical pathogens. 3, 1 Risk factors include structural lung disease (bronchiectasis), severe COPD with frequent steroid/antibiotic use, and prior antibiotic therapy. 3
Cystic Fibrosis Patients
Use higher doses due to altered pharmacokinetics: ceftazidime 150-250 mg/kg/day or meropenem 60-120 mg/kg/day PLUS tobramycin ~10 mg/kg/day IV once daily. 1 For maintenance therapy, use inhaled tobramycin 300mg twice daily or colistin 1-2 million units twice daily. 1
Urinary Tract Infections
Ciprofloxacin 400mg IV every 8 hours or 750mg PO twice daily can be used as monotherapy for uncomplicated UTIs, but combination therapy is needed for complicated infections. 2, 5
Difficult-to-Treat Resistant Pseudomonas
For multidrug-resistant strains, newer agents are preferred:
- Ceftolozane/tazobactam: 1.5-3g IV every 8 hours (preferred for pneumonia) 1, 6
- Ceftazidime/avibactam: 2.5g IV every 8 hours 1, 6
- Imipenem/cilastatin/relebactam: 1.25g IV every 6 hours 2, 6
- Cefiderocol: Preferred for metallo-β-lactamase producers (70.8% clinical cure rate) 1, 6
These agents should be used when there is resistance to standard β-lactams or when metallo-β-lactamases are present. 1, 6
Treatment Duration
- Standard duration: 7-14 days for most infections, including nosocomial/ventilator-associated pneumonia 1, 2
- Bronchiectasis exacerbations: 14 days (not 12 days) with ciprofloxacin 750mg twice daily 1
- Longer courses: Required for immunocompromised hosts or when source control is inadequate 1
De-escalate to monotherapy once susceptibility results are available if the patient is improving and the organism is susceptible. 1, 2
Critical Pitfalls to Avoid
- Never use aminoglycoside monotherapy for empirical coverage or bacteremia—rapid resistance emergence occurs 2
- Never underdose—use maximum recommended doses for Pseudomonas infections, as standard doses may be inadequate 1
- Never extend oral ciprofloxacin monotherapy beyond 14 days—this promotes resistance without proven benefit 1
- Never assume vancomycin adds Pseudomonas coverage—it only covers Gram-positive organisms (MRSA) and has zero activity against Gram-negatives 1, 2
- Avoid imipenem/cilastatin when other carbapenems are available due to higher rates of allergic reactions 1
- Monitor for resistance development—Pseudomonas can develop resistance fairly rapidly during treatment, so perform culture and susceptibility testing periodically 4, 5
Special Dosing for Pediatrics
For pediatric patients with Pseudomonas infections: