What antibiotics are recommended for treating Pseudomonas infections?

Antibiotic Treatment for Pseudomonas Infections

For Pseudomonas aeruginosa infections, use combination therapy with an antipseudomonal β-lactam (piperacillin-tazobactam, ceftazidime, cefepime, or meropenem) PLUS either ciprofloxacin or an aminoglycoside (tobramycin preferred over gentamicin) for severe infections, nosocomial pneumonia, or high-risk patients. 1, 2

First-Line Antipseudomonal β-Lactams

The following agents provide robust coverage against P. aeruginosa and should form the backbone of therapy:

• 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) 1, 2
• Cefepime: 2g IV every 8-12 hours (or 100-150 mg/kg/day divided in 2-3 doses, maximum 6g daily) 1, 2
• Meropenem: 1g IV every 8 hours (or 60-120 mg/kg/day divided in 3 doses, maximum 6g daily) 1, 2

Avoid imipenem/cilastatin as it has higher rates of allergic reactions in this population. 1

When to Use Combination Therapy vs. Monotherapy

Combination therapy is mandatory for:

• Severe infections or sepsis 1, 2
• Nosocomial or ventilator-associated pneumonia 1, 3
• ICU-level illness 1
• Documented or suspected Pseudomonas in community-acquired pneumonia requiring ICU admission 1
• Structural lung disease (bronchiectasis, severe COPD with frequent exacerbations) 1
• Prior antibiotic exposure 1

Monotherapy may be considered only for:

• Mild-to-moderate infections in immunocompetent patients with confirmed susceptibility 4
• After susceptibility results confirm sensitivity and clinical stability is achieved 2

The rationale for combination therapy is to prevent inappropriate initial therapy and reduce emergence of resistance, not necessarily to achieve synergy. 1 Once susceptibilities are known, de-escalation to monotherapy is appropriate if the organism is susceptible. 2

Second Agent Selection

Add one of the following to your β-lactam:

Fluoroquinolone Option:

• Ciprofloxacin: 400mg IV every 8-12 hours OR 750mg PO every 12 hours 1, 2, 4
• Levofloxacin: 750mg IV/PO once daily (less preferred than ciprofloxacin for Pseudomonas) 1, 3

Aminoglycoside Option:

• Tobramycin: 10 mg/kg IV once daily (preferred over gentamicin due to lower nephrotoxicity) 1, 2
• Gentamicin: Less desirable due to higher nephrotoxicity 1

Use the aminoglycoside-containing regimen if the patient has recently received an oral fluoroquinolone. 1

Dosing Considerations and Common Pitfalls

Critical dosing errors to avoid:

• Underdosing is common in critically ill patients. Standard intermittent bolus dosing of ceftazidime (2g every 8h) resulted in subtherapeutic levels in 30-40% of critically ill patients in one study, with trough levels below MIC for P. aeruginosa. 5 Consider extended infusion (3-4 hours) or continuous infusion for severe infections. 6

• Once-daily aminoglycoside dosing is equally efficacious and less toxic than three-times-daily dosing. 2 Target peak tobramycin levels of 25-35 mg/mL with once-daily dosing. 1

• Monitor aminoglycoside levels, renal function, and auditory function to minimize nephrotoxicity and ototoxicity. 1

Treatment Duration

• Standard duration: 7-14 days for most Pseudomonas infections 2, 4
• Nosocomial/ventilator-associated pneumonia: 7-14 days 1
• Limit to 4-7 days if source control is adequate 2
• Bone/joint infections: 6 weeks 4

Site-Specific Considerations

Respiratory Infections (Pneumonia, CF, COPD):

• For community-acquired pneumonia with Pseudomonas risk factors: Use antipseudomonal β-lactam + (ciprofloxacin OR aminoglycoside) + azithromycin to cover atypical pathogens 1
• For CF patients: Combination therapy is standard; inhaled tobramycin (300mg twice daily) or colistin (1-2 million units twice daily) can be added for maintenance therapy 1, 2

Nosocomial Pneumonia:

• When Pseudomonas is documented or presumptive, add an antipseudomonal β-lactam (ceftazidime or piperacillin/tazobactam) even if already using levofloxacin. 3 In the pivotal nosocomial pneumonia trial, 88% of levofloxacin-treated patients with documented P. aeruginosa received ceftazidime or piperacillin/tazobactam as adjunctive therapy. 3

Oral Therapy Options

Ciprofloxacin is the only reliable oral option for Pseudomonas:

• 750mg PO every 12 hours for 10-14 days 4
• Switch from IV to oral by day 3 if clinically stable 4
• Monotherapy is appropriate only for mild-to-moderate infections with confirmed susceptibility 4
• Resistance can develop rapidly during monotherapy; repeat cultures are essential 3, 7

Levofloxacin has activity against P. aeruginosa but is less preferred than ciprofloxacin. 3 The FDA label notes that "some isolates of Pseudomonas aeruginosa may develop resistance fairly rapidly during treatment with levofloxacin." 3

Resistance Patterns and Salvage Therapy

If resistance develops or for multidrug-resistant strains:

• Amikacin and imipenem remain effective as salvage therapy against isolates resistant to one or two agents 8
• Ceftolozane/tazobactam or ceftazidime/avibactam for difficult-to-treat resistant strains 2
• Cefiderocol for metallo-β-lactamase producers (70.8% clinical cure rate) 2
• Fosfomycin only in combination with another active agent; never as monotherapy due to rapid resistance emergence within 24 hours 9, 10

Monitor susceptibility patterns with repeat cultures during therapy to detect emerging resistance. 3, 7

Special Populations

Pediatric Dosing:

• Ciprofloxacin: 10-20 mg/kg/dose PO every 12 hours (max 750mg/dose) OR 10 mg/kg/dose IV every 8-12 hours (max 400mg/dose) 4
• Reserve fluoroquinolone use for situations where benefit outweighs cartilage toxicity risk 4

Renal Impairment:

• Adjust β-lactam and aminoglycoside doses based on creatinine clearance 2
• Extended dosing intervals for aminoglycosides with therapeutic drug monitoring 1