What classes of antibiotics are effective against Pseudomonas aeruginosa infections?

Anti-Pseudomonas Antibiotics and Their Classes

For Pseudomonas aeruginosa infections, the most effective antibiotics span five major classes: antipseudomonal β-lactams (penicillins, cephalosporins, carbapenems), fluoroquinolones, aminoglycosides, monobactams, and polymyxins. 1

Antipseudomonal β-Lactams

Extended-Spectrum Penicillins

• Piperacillin-tazobactam is a first-line agent dosed at 3.375-4.5g IV every 6 hours for most infections 1
• This combination provides excellent antipseudomonal coverage and is recommended for both non-severe and severe infections when combined with a second agent 2, 1

Antipseudomonal Cephalosporins

• Ceftazidime (third-generation): 2g IV every 8 hours or 150-250 mg/kg/day divided in 3-4 doses (maximum 12g daily) 1
• Cefepime (fourth-generation): 2g IV every 8-12 hours or 100-150 mg/kg/day divided in 2-3 doses (maximum 6g daily) 1
• These agents have robust activity against P. aeruginosa and are preferred over non-antipseudomonal cephalosporins like ceftriaxone or cefazolin, which have NO activity 1, 3

Carbapenems

• Meropenem: 1g IV every 8 hours (standard) or 60-120 mg/kg/day divided in 3 doses (maximum 6g daily), with escalation to 3 × 2g in 3-hour infusions for severe cases 1
• Imipenem-cilastatin: 1g IV every 8 hours or 50-100 mg/kg/day divided in 3-4 doses (maximum 4g daily) 1
• Meropenem is generally preferred over imipenem due to lower rates of allergic reactions 1
• Critical pitfall: Ertapenem explicitly lacks antipseudomonal coverage and should NEVER be used 1, 3

Fluoroquinolones

• Ciprofloxacin is the ONLY fluoroquinolone with reliable antipseudomonal activity 3
• Oral dosing: 750mg twice daily (high-dose regimen specifically for Pseudomonas) 1, 3
• IV dosing: 400mg every 8 hours 1
• Levofloxacin and moxifloxacin do NOT provide adequate Pseudomonas coverage and should not be used 3
• Cross-resistance exists between ciprofloxacin and levofloxacin; strains resistant to one are resistant to both 3

Aminoglycosides

• Tobramycin (preferred): 5-7 mg/kg IV daily with target peak levels of 25-35 mg/mL 1
• Amikacin (alternative): 15-20 mg/kg IV daily 1
• Gentamicin: ~10 mg/kg/day IV, though tobramycin is preferred due to lower nephrotoxicity 1, 4
• Once-daily dosing is equally efficacious and less toxic than three-times-daily dosing 1
• Therapeutic drug monitoring is mandatory to optimize efficacy and minimize nephrotoxicity and ototoxicity 1

Monobactams

• Aztreonam: 2g IV every 8 hours 1
• This is the preferred option for patients with severe penicillin allergy requiring antipseudomonal coverage 1

Polymyxins

• Colistin (polymyxin E): 1-2 million units twice daily 1
• Reserved for multidrug-resistant strains when other options have failed 1, 5
• Can be administered intravenously or via inhalation for respiratory infections 1

Newer Agents for Resistant Strains

• Ceftolozane-tazobactam and ceftazidime-avibactam are first-line options for difficult-to-treat resistant Pseudomonas 1
• Cefiderocol is recommended for metallo-β-lactamase producers, with 70.8% clinical cure rates 1

Inhaled Antibiotics (Respiratory Infections)

• Tobramycin: 300mg twice daily for maintenance therapy in cystic fibrosis or chronic respiratory infections 1
• Colistin: 1-2 million units twice daily for respiratory infections 1
• These reduce exacerbations and maintain lung function in chronic colonization 1

When to Use Combination Therapy

Combination therapy with an antipseudomonal β-lactam PLUS either an aminoglycoside OR ciprofloxacin is mandatory for: 1

• Severe infections or septic shock 1
• Ventilator-associated or nosocomial pneumonia 2, 1
• Structural lung disease (bronchiectasis, cystic fibrosis) 2, 1
• Prior IV antibiotic use within 90 days 1
• Documented Pseudomonas on Gram stain 1
• High local prevalence of multidrug-resistant strains 1

Combination therapy delays resistance development compared to monotherapy and should be used until susceptibility results allow de-escalation 2, 1

Treatment Duration

• Standard duration: 7-14 days for most infections including nosocomial/ventilator-associated pneumonia 1
• Extended therapy: 10-14 days for complicated infections or immunocompromised hosts 5
• Limit to 4-7 days if source control is adequate 1

Critical Pitfalls to Avoid

• Never assume a β-lactam has antipseudomonal activity: Ceftriaxone, cefazolin, ampicillin-sulbactam, and ertapenem do NOT cover Pseudomonas despite being broad-spectrum 1, 3
• Avoid monotherapy with fluoroquinolones in severe infections due to rapid resistance development 3
• Underdosing leads to treatment failure: Use maximum recommended doses, especially for severe infections 1
• Always check local resistance patterns before selecting empiric therapy 1, 5
• Do not use levofloxacin or moxifloxacin when Pseudomonas coverage is needed—only ciprofloxacin is effective 3

Special Population Considerations

Cystic Fibrosis Patients

• Antibiotic selection must be based on susceptibility testing due to higher resistance rates 2, 5
• Early aggressive treatment of intermittent colonization with systemic plus inhaled antibiotics delays chronic infection 1
• Maintenance inhaled therapy (tobramycin or colistin) reduces exacerbations 1

Urinary Tract Infections

• Ciprofloxacin is first-line oral treatment 5
• Piperacillin-tazobactam is preferred for IV therapy in severe cases 5
• Combination therapy may be needed for immunocompromised patients 5