What is the recommended treatment for a patient with a Gram-negative skin infection, considering potential allergies, impaired renal function, and immunocompromised status?

Treatment of Gram-Negative Skin Infections

For gram-negative skin infections, incision and drainage is the primary treatment when an abscess is present, combined with empiric broad-spectrum antibiotics covering both gram-positive and gram-negative organisms, with specific regimens adjusted based on severity, immunocompromised status, and renal function. 1

Primary Treatment Approach

Source control through incision and drainage is mandatory for all cutaneous abscesses and cannot be replaced by antibiotics alone. 1 Drainage should be performed promptly, with repeat imaging if bacteremia persists to identify undrained foci. 1

Empiric Antibiotic Selection

Standard Regimens for Gram-Negative Coverage

The choice of empiric therapy depends on infection severity and patient risk factors:

For severe infections or when Pseudomonas aeruginosa is suspected, antipseudomonal agents are essential as gram-negative bacilli are associated with the highest infection-associated mortality. 1

Recommended first-line regimens include: 2, 1

• Ceftazidime (1-2 g IV every 8 hours)
• Cefepime (2 g IV every 8-12 hours)
• Piperacillin-tazobactam (3.375-4.5 g IV every 6-8 hours)
• Carbapenems (meropenem 1 g IV every 8 hours or imipenem)

When treating skin infections caused by Pseudomonas aeruginosa specifically, higher doses are required: ceftazidime 2 g every 8 hours or meropenem 1 g every 8 hours. 3

For less severe infections without Pseudomonas risk, alternatives include: 2

• Gentamicin (1.5 mg/kg IV every 8 hours)
• Ciprofloxacin (400 mg IV every 8-12 hours)
• Doxycycline (100 mg IV/PO twice daily)

Special Populations Requiring Modified Regimens

Immunocompromised patients require immediate broad-spectrum coverage due to high mortality risk from gram-negative infections and should receive vancomycin plus an antipseudomonal agent (piperacillin-tazobactam, cefepime, or carbapenem). 2, 1

Perianal or perirectal abscesses require coverage for gram-negative, gram-positive, and anaerobic bacteria with piperacillin-tazobactam or a carbapenem. 1, 4

Renal Impairment Dosing Adjustments

For patients with creatinine clearance ≤50 mL/min, dose reduction is mandatory to prevent toxicity. 3

Meropenem dosing adjustments for renal impairment: 3

• CrCl >50 mL/min: 500 mg-1 g every 8 hours (standard dose)
• CrCl 26-50 mL/min: Standard dose every 12 hours
• CrCl 10-25 mL/min: Half dose every 12 hours
• CrCl <10 mL/min: Half dose every 24 hours

Aminoglycosides (gentamicin) require particularly careful monitoring in renal impairment with therapeutic drug monitoring and dose adjustment based on levels. 2

Carbapenem-Resistant Gram-Negative Bacilli

For carbapenem-resistant gram-negative infections, polymyxin combination therapy is recommended over monotherapy, with careful monitoring of renal function. 2

Preferred combinations include: 2

• Colistin plus meropenem (if meropenem MIC ≤8 mg/L for CRE or ≤32 mg/L for CRAB, using extended 3-hour infusion)
• Colistin plus rifampicin
• Colistin plus fosfomycin

Therapeutic drug monitoring should be performed for polymyxins where possible, and ototoxic/nephrotoxic drugs must be avoided in combination. 2

Alternative agents for carbapenem-resistant organisms: 2

• Ceftazidime-avibactam
• Tigecycline
• Sulbactam-containing combinations

Treatment Duration and Monitoring

The standard duration is 7-14 days for most bacterial skin and soft tissue infections, but may be shortened to 24-48 hours if only mild systemic signs are present and adequate drainage is achieved. 1, 4

Treatment should be switched to oral therapy once the patient is clinically improved, afebrile for 48-72 hours, and bacteremia has cleared. 1, 4

De-escalation of antibiotic therapy should be based on clinical improvement, cultured pathogens, and antimicrobial susceptibility results. 2

Critical Pitfalls to Avoid

Never rely on antibiotics alone without drainage for abscesses, as source control is paramount and antibiotics are insufficient without it. 1

Do not delay gram-negative coverage in high-risk patients (immunocompromised, diabetic, perirectal location), as mortality is highest with gram-negative bacteremia, particularly Pseudomonas aeruginosa. 1

Avoid vancomycin in patients with renal impairment or when MRSA isolates show vancomycin MIC ≥1.5 mg/L; use daptomycin or linezolid instead. 2

Do not use standard doses of antipseudomonal agents when Pseudomonas is suspected—higher doses are required (ceftazidime 2 g every 8 hours or meropenem 1 g every 8 hours). 3, 5

The choice of anti-gram-negative treatment must be based on local prevalence of ESBL-producing Enterobacteriaceae and multidrug-resistant organisms. 2