What are the antipseudomonal agents available in both intravenous (IV) and oral formulations?

Antipseudomonal Agents: IV and Oral Formulations

Ciprofloxacin is the only fluoroquinolone with reliable oral and IV antipseudomonal activity, while levofloxacin has weaker activity against Pseudomonas aeruginosa and should be considered a second-line oral option. 1, 2

Oral Antipseudomonal Agents

Fluoroquinolones (Primary Oral Option)

• Ciprofloxacin 750 mg orally every 12 hours is the preferred oral antipseudomonal agent, offering superior activity compared to other fluoroquinolones 1, 2
• Ciprofloxacin achieves comparable serum levels with oral and IV administration due to high bioavailability, and penetrates well into lung tissue with sputum concentrations reaching 46-90% of serum levels 1, 3
• Levofloxacin has activity against P. aeruginosa but is generally less potent than ciprofloxacin, with 75% of isolates susceptible compared to 82% for ciprofloxacin 3, 4, 5
• Ofloxacin is the least active fluoroquinolone against Pseudomonas and should not be relied upon 5

Important Limitations of Oral Therapy

• Oral ciprofloxacin monotherapy should be limited to mild-to-moderate infections in immunocompetent patients with confirmed susceptibility 2
• Rapid emergence of resistance is a significant concern with fluoroquinolone monotherapy, particularly more problematic than with IV combination therapy 1
• For seriously affected patients, conventional IV therapy is significantly better than oral quinolone treatment 1

Intravenous Antipseudomonal Agents

Beta-Lactams (First-Line IV Options)

• Piperacillin-tazobactam 3.375-4.5g IV every 6 hours is the preferred first-line agent for most Pseudomonas infections 6, 3
• Ceftazidime 2g IV every 8 hours (or 150-250 mg/kg/day divided in 3-4 doses, maximum 12g daily) 6, 3
• Cefepime 2g IV every 8-12 hours (or 100-150 mg/kg/day divided in 2-3 doses, maximum 6g daily) 6, 3
• Meropenem 1g IV every 8 hours (or 60-120 mg/kg/day divided in 3 doses, maximum 6g daily, can escalate to 3 × 2g in severe cases) 6, 3
• Imipenem/cilastatin 1g IV every 8 hours (or 50-100 mg/kg/day divided in 3-4 doses, maximum 4g daily), though less preferred due to higher allergic reaction rates 6, 3
• Aztreonam 2g IV every 8 hours is the only monobactam with antipseudomonal activity and can be used in severe penicillin allergy 3

Fluoroquinolones (IV Formulations)

• Ciprofloxacin 400mg IV every 8-12 hours is available for patients unable to take oral therapy 1, 2, 3
• Levofloxacin 750mg IV daily is less potent but available IV 3, 7

Aminoglycosides (Combination Therapy)

• Tobramycin 5-7 mg/kg IV daily (or ~10 mg/kg/day) is the preferred aminoglycoside, with once-daily dosing equally efficacious and less toxic than three-times-daily dosing 6, 3
• Amikacin 15-20 mg/kg IV daily is an alternative aminoglycoside option 6, 3
• Gentamicin is less desirable than tobramycin due to higher nephrotoxicity 1, 3
• All aminoglycosides require therapeutic drug monitoring with target tobramycin peak levels of 25-35 mg/mL 6, 3

Polymyxins (Multidrug-Resistant Strains)

• Colistin 1-2 million units IV (5mg CBA/kg loading dose, then 2.5mg CBA maintenance) for multidrug-resistant strains 6, 3

Agents Available in BOTH IV and Oral Formulations

Only fluoroquinolones are available in both IV and oral formulations with antipseudomonal activity:

• Ciprofloxacin: 400mg IV every 8-12 hours OR 750mg orally every 12 hours 1, 2, 3
• Levofloxacin: 750mg IV or orally daily (though less potent against Pseudomonas) 1, 3, 7

Critical Agents That LACK Antipseudomonal Activity

Avoid these common pitfalls—the following agents do NOT cover Pseudomonas despite being broad-spectrum:

• Ceftriaxone and cefazolin have no antipseudomonal activity 6, 3
• Ertapenem explicitly lacks antipseudomonal coverage despite being a carbapenem 6, 3
• Ampicillin/sulbactam has no clinically relevant activity against P. aeruginosa 6
• Most streptococcal-focused, enterococcal, and anaerobic coverage drugs are ineffective 6

When to Use Combination Therapy vs. Monotherapy

Monotherapy Appropriate For:

• Mild-to-moderate infections in immunocompetent patients with confirmed susceptibility 2
• Non-severe infections after susceptibility results confirm single-agent activity 3

Combination Therapy Required For:

• Critically ill patients or septic shock 6, 3
• Ventilator-associated or nosocomial pneumonia 6, 3
• Structural lung disease (bronchiectasis, cystic fibrosis) 6, 3
• Prior IV antibiotic use within 90 days 6, 3
• Documented Pseudomonas on Gram stain 6
• High local prevalence of multidrug-resistant strains 6

Recommended Combinations:

• Antipseudomonal β-lactam PLUS ciprofloxacin 1, 6, 3
• Antipseudomonal β-lactam PLUS aminoglycoside (tobramycin preferred) 6, 3
• Combination therapy delays resistance development compared to monotherapy 6, 3

Treatment Duration and Transition Strategy

• Standard duration: 7-14 days for most Pseudomonas infections, with 10-14 days preferred for pneumonia or bloodstream infections 2, 6, 3
• Switch from IV to oral ciprofloxacin by day 3 if clinically stable, as oral bioavailability matches IV levels 2
• De-escalate to monotherapy once susceptibility results are available if the patient is improving and the organism is susceptible 1, 6, 3

Special Dosing Considerations

• Cystic fibrosis patients require higher doses due to altered pharmacokinetics: ceftazidime 150-250 mg/kg/day, meropenem 60-120 mg/kg/day 6, 3
• Maximum recommended doses should be used for severe infections to avoid underdosing and treatment failure 6, 3
• Aminoglycoside monotherapy should NEVER be used for empirical coverage or bacteremia due to rapid resistance emergence 3