Treatment of Pseudomonas aeruginosa Skin and Soft-Tissue Infections
For Pseudomonas aeruginosa skin infections, use meropenem 1 gram IV every 8 hours or cefepime 2 grams IV every 8 hours as monotherapy for 7-10 days, with dose adjustment required for renal impairment. 1, 2
Antibiotic Selection Algorithm
First-Line IV Therapy for Confirmed Pseudomonas Skin Infections
Meropenem is the preferred carbapenem, dosed at 1 gram IV every 8 hours when treating infections caused by Pseudomonas aeruginosa, administered as a 15-30 minute infusion. 1 For complicated skin and skin structure infections specifically caused by P. aeruginosa, the FDA label explicitly recommends this higher dose rather than the standard 500 mg dose used for other pathogens. 1
Cefepime is an equally effective alternative, dosed at 2 grams IV every 8 hours for moderate to severe skin infections when P. aeruginosa is the causative organism, administered over approximately 30 minutes. 2 This represents the maximum recommended dose for antipseudomonal coverage in skin infections. 2
Piperacillin-tazobactam can be used at 3.375-4.5 grams IV every 6 hours, though this is typically reserved for polymicrobial infections or when broader anaerobic coverage is needed. 3, 4
Oral Therapy Options (Limited Role)
Ciprofloxacin 500-750 mg orally twice daily is the only oral option with reliable P. aeruginosa activity for skin infections, but should be reserved for step-down therapy after initial IV treatment or for mild infections in immunocompetent patients. 3, 5 Clinical cure with bacterial eradication was achieved in 75% of patients with P. aeruginosa skin and soft tissue infections treated with ciprofloxacin monotherapy, though this was limited to patients with normal host defense mechanisms. 5
Levofloxacin and moxifloxacin have antipseudomonal activity but are less potent than ciprofloxacin and should not be first-line choices. 3
Combination Therapy Considerations
Combination therapy is NOT routinely recommended for skin infections unless the patient is severely immunocompromised, has bacteremia, or has failed monotherapy. 6, 7 Historically, combinations of aminoglycosides (amikacin or tobramycin) with beta-lactams were advocated, but current evidence supports monotherapy for localized skin infections in immunocompetent hosts. 7
When combination therapy is indicated, use a beta-lactam backbone (meropenem, cefepime, or piperacillin-tazobactam) PLUS an aminoglycoside (tobramycin or amikacin). 8, 7 Piperacillin-tazobactam plus an aminoglycoside achieved the highest susceptibility rate (93.3%) in recent U.S. hospital data, though this still falls short of the 95% coverage goal. 8
Adding a fluoroquinolone to a beta-lactam results in lower susceptibility rates than adding an aminoglycoside and should be avoided for empiric combination therapy. 8
Dosing Adjustments for Renal Impairment
Meropenem Renal Dosing
For creatinine clearance 26-50 mL/min: administer the recommended dose (1 gram for P. aeruginosa) every 12 hours instead of every 8 hours. 1
For creatinine clearance 10-25 mL/min: administer one-half the recommended dose (500 mg) every 12 hours. 1
For creatinine clearance <10 mL/min: administer one-half the recommended dose (500 mg) every 24 hours. 1
Cefepime Renal Dosing
Adjust dose in patients with creatinine clearance ≤60 mL/min according to institutional protocols, as specific adjustments are detailed in the full prescribing information. 2
Treatment Duration
Treat for 7-10 days for uncomplicated skin infections, extending to 14 days only for complicated infections with deep tissue involvement, abscess formation, or immunocompromise. 3 The standard 5-day duration used for typical cellulitis does NOT apply to Pseudomonas infections, which require longer courses. 4
Special Populations
Pediatric Dosing (≥3 months)
Meropenem: 20 mg/kg (up to 1 gram maximum) IV every 8 hours for complicated skin infections caused by P. aeruginosa. 1
Cefepime: 50 mg/kg per dose IV every 8 hours (not every 12 hours) for P. aeruginosa coverage, up to a maximum of 2 grams per dose. 2
Immunocompromised Patients
Mandatory combination therapy with a beta-lactam PLUS an aminoglycoside or fluoroquinolone is required for neutropenic patients or those with severe immunosuppression. 3, 7 Mortality rates in rapidly fatal disease remain as high as 85% despite antibiotic therapy, making aggressive combination regimens essential. 7
Novel Agents for Resistant Strains
Ceftolozane-tazobactam is a newer beta-lactam/beta-lactamase inhibitor with powerful anti-P. aeruginosa activity, particularly useful for MDR and XDR strains in patients with impaired renal function. 9 This agent was successfully used as monotherapy in complicated skin infections caused by resistant Pseudomonas without worsening renal function. 9
Cefiderocol, a novel siderophore cephalosporin, shows very promising results against P. aeruginosa and represents a future treatment option for resistant strains. 6
Critical Pitfalls to Avoid
Do NOT use oral antibiotics as initial therapy for serious Pseudomonas skin infections—IV therapy is mandatory for reliable tissue penetration and bactericidal activity. 5, 6
Do NOT use standard cellulitis doses (e.g., cefepime 1 gram every 12 hours or meropenem 500 mg every 8 hours)—Pseudomonas requires maximum dosing for adequate coverage. 1, 2
Do NOT rely on single-agent susceptibility testing alone—combination antibiograms should guide empiric therapy in high-risk patients, as single agents fail to achieve 95% coverage in U.S. hospitals. 8
Monitor for emergence of resistance during therapy, as decreasing susceptibility to fluoroquinolones (MIC increase from ≤0.5 to 2-16 mcg/mL) was documented in 23% of patients treated with ciprofloxacin monotherapy. 5
Avoid aminoglycoside monotherapy—nephrotoxicity and ototoxicity risks are increased, and beta-lactams provide superior outcomes when used alone or in combination. 2