Which antibiotics provide coverage against Pseudomonas aeruginosa?

Antibiotics with Pseudomonas Coverage

The first-line antipseudomonal antibiotics are piperacillin-tazobactam, ceftazidime, cefepime, meropenem, and imipenem, with ciprofloxacin as the preferred fluoroquinolone option. 1, 2

First-Line Antipseudomonal β-Lactams

The following β-lactam antibiotics provide reliable coverage against Pseudomonas aeruginosa:

• Piperacillin-tazobactam 4.5g IV every 6 hours – This is the most commonly recommended first-line agent, with extended infusion (4-hour infusion) preferred for critically ill patients to maximize time above MIC 1, 2
• Ceftazidime 2g IV every 8 hours – Highly active antipseudomonal cephalosporin, though less reliable than in the past due to emerging resistance 1, 2
• Cefepime 2g IV every 8 hours – Excellent antipseudomonal activity with broader gram-positive coverage than ceftazidime 1, 2
• Meropenem 1g IV every 8 hours – Superior carbapenem with documented activity against non-fermentative gram-negatives including P. aeruginosa 1, 2
• Imipenem 500mg IV every 6 hours – Alternative carbapenem option, though some guidelines suggest avoiding it due to higher allergic reaction rates 1, 2

Fluoroquinolones

• Ciprofloxacin 400mg IV every 8 hours or 750mg PO twice daily – This is the preferred and most potent fluoroquinolone for Pseudomonas, with superior in-vitro activity compared to levofloxacin 1, 2
• Levofloxacin 750mg IV/PO daily – Less potent than ciprofloxacin but acceptable as second-line option 1, 2

Aminoglycosides

• Tobramycin 5-7 mg/kg IV daily – Preferred aminoglycoside due to lower nephrotoxicity compared to gentamicin, with target peak levels of 25-35 mg/mL 1, 2
• Amikacin 15-20 mg/kg IV daily – Alternative aminoglycoside with activity against some tobramycin-resistant strains 1, 2
• Gentamicin 5-7 mg/kg IV daily – Less desirable than tobramycin due to higher nephrotoxicity and ototoxicity 2

Monobactam

• Aztreonam 2g IV every 8 hours – The only antipseudomonal option for patients with severe β-lactam allergy, as it does not cross-react with penicillins or cephalosporins 1, 2

Inhaled Antibiotics (for Chronic Respiratory Infections)

• Tobramycin 300mg inhaled twice daily – Maintenance therapy for cystic fibrosis or chronic bronchiectasis with P. aeruginosa colonization 2
• Colistin 1-2 million units inhaled twice daily – Alternative inhaled agent for maintenance therapy or multidrug-resistant strains 2

When to Use Combination Therapy

Combination therapy with an antipseudomonal β-lactam PLUS either an aminoglycoside or ciprofloxacin is mandatory in the following scenarios: 1, 2

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

The rationale for combination therapy is to prevent treatment failure, reduce resistance development, and potentially achieve synergistic killing. 1, 2

Newer Agents for Resistant Strains

For multidrug-resistant or carbapenem-resistant Pseudomonas:

• Ceftolozane-tazobactam – First-line for difficult-to-treat resistant strains 2
• Ceftazidime-avibactam – Alternative for carbapenem-resistant isolates 2
• Cefiderocol – For metallo-β-lactamase producers, with 70.8% clinical cure rates 2

Critical Antibiotics That Do NOT Cover Pseudomonas

Never assume a β-lactam has antipseudomonal activity. The following broad-spectrum agents have NO activity against Pseudomonas despite being commonly used: 2

• Ceftriaxone
• Cefazolin
• Ampicillin-sulbactam
• Ertapenem (Group 1 carbapenem explicitly lacks antipseudomonal coverage)
• Most streptococcal-focused and enterococcal agents

Treatment Duration

• Standard duration: 7-14 days depending on infection site and severity 1, 2
• Pneumonia or bloodstream infections: 10-14 days 2
• Uncomplicated UTI: 7 days 3
• Complicated UTI or pyelonephritis: 7-10 days 3

Common Pitfalls to Avoid

• Underdosing leads to treatment failure – Use maximum recommended doses for severe infections, especially for Pseudomonas which requires higher concentrations than other gram-negatives 2
• Fluoroquinolone monotherapy for severe infections – High risk of resistance development; reserve for uncomplicated cases only 2, 4
• Assuming all β-lactams cover Pseudomonas – Many broad-spectrum agents lack activity 2
• Not checking local antibiograms – Resistance patterns vary significantly by institution and should guide empiric therapy 2
• Stopping combination therapy too early – Continue dual coverage until susceptibility results allow safe de-escalation 2

De-escalation Strategy

Once susceptibility results are available and the patient is clinically improving, therapy can be narrowed to monotherapy if the organism is susceptible to a single agent. 2, 3 Continue treatment for the full duration even after de-escalation to prevent resistance development. 3