What IV antibiotic treats Pseudomonas aeruginosa?

IV Antibiotics for Pseudomonas aeruginosa

For most Pseudomonas aeruginosa infections, start with an antipseudomonal β-lactam (ceftazidime, cefepime, piperacillin-tazobactam, or meropenem) as first-line IV therapy, and add a second agent (aminoglycoside or ciprofloxacin) for severe infections, nosocomial pneumonia, or high-risk patients. 1

First-Line Antipseudomonal β-Lactams

The following agents have established efficacy against P. aeruginosa:

• Ceftazidime: 150-250 mg/kg/day divided in 3-4 doses (maximum 12g daily) 1
• Cefepime: 100-150 mg/kg/day divided in 2-3 doses (maximum 6g daily) 1
• Piperacillin-tazobactam: 3.375-4.5g IV every 6 hours for non-severe infections; 4.5g every 6 hours for nosocomial pneumonia 2, 1
• Meropenem: 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

These β-lactams achieve adequate serum and tissue concentrations when dosed appropriately, though higher doses are required for P. aeruginosa compared to other gram-negative infections. 1

When to Add Combination Therapy

Combination therapy with two antipseudomonal agents from different classes is mandatory in specific clinical scenarios:

• Nosocomial/ventilator-associated pneumonia: Always combine an antipseudomonal β-lactam with an aminoglycoside (typically tobramycin) or ciprofloxacin 2, 1
• Severe infections or sepsis: Add a second agent to prevent inadequate treatment and reduce resistance development 1
• High-risk patients: Immunocompromised hosts or those with known multidrug-resistant strains benefit from dual therapy 1

The FDA label for piperacillin-tazobactam explicitly states that nosocomial pneumonia caused by P. aeruginosa "should be treated in combination with an aminoglycoside." 2

Aminoglycoside Dosing

Tobramycin is the preferred aminoglycoside:

• Initial dosing: ~10 mg/kg/day IV, with once-daily dosing shown to be less toxic and equally efficacious as three-times-daily dosing 3
• Therapeutic drug monitoring is essential to optimize efficacy and minimize ototoxicity and nephrotoxicity 1
• Once-daily tobramycin combined with ceftazidime has been validated as safe and effective 3

Fluoroquinolone Option

Ciprofloxacin IV provides an alternative second agent:

• Dosing: 400 mg IV every 8-12 hours 4, 5
• FDA-approved for P. aeruginosa infections including lower respiratory infections, skin/soft tissue infections, bone/joint infections, and complicated intra-abdominal infections 4
• Can be switched to oral (750 mg twice daily) by day 3 if clinically stable 5

Carbapenems for Resistant Strains

Meropenem is preferred over imipenem for P. aeruginosa due to superior activity:

• Meropenem is a Group 2 carbapenem with documented activity against non-fermentative gram-negative bacilli including P. aeruginosa 1
• For severe infections, combine meropenem with ciprofloxacin or an aminoglycoside to prevent resistance 1

Critical caveat: Ertapenem has NO activity against P. aeruginosa and should never be used. 1

Newer Agents for Difficult-to-Treat Resistant P. aeruginosa

When first-line agents fail due to resistance:

• Ceftolozane-tazobactam and ceftazidime-avibactam are preferred initial options for difficult-to-treat resistant strains 6, 1
• Ceftolozane-tazobactam is specifically preferred for P. aeruginosa pneumonia over ceftazidime-avibactam 6
• Cefiderocol is reserved for metallo-β-lactamase producers, with 70.8% clinical cure rates 1, 6
• Imipenem-relebactam may retain activity when resistance exists to ceftolozane-tazobactam and ceftazidime-avibactam (excluding metallo-β-lactamases) 6

Treatment Duration

• Standard duration: 7-14 days depending on infection site and severity 1
• Nosocomial pneumonia: 7-14 days 2
• Bone/joint infections: 6 weeks 5
• Limit to 4-7 days for intra-abdominal infections unless source control is inadequate 1

Common Pitfalls to Avoid

• Underdosing: Standard doses may be inadequate for P. aeruginosa; use maximum recommended doses 3, 1
• Monotherapy in severe infections: This leads to treatment failure and rapid resistance development 1
• Ignoring local resistance patterns: Always obtain cultures and susceptibility testing before finalizing therapy 1
• Inadequate monitoring: Aminoglycosides require therapeutic drug monitoring to prevent toxicity while maintaining efficacy 1
• Using ertapenem or ampicillin-sulbactam: These agents have NO clinically relevant activity against P. aeruginosa 1