What is the recommended dosing for Unasyn (ampicillin/sulbactam) for skin and soft tissue infections?

Unasyn Dosing for Skin and Soft Tissue Infections

For skin and soft tissue infections in adults, Unasyn (ampicillin/sulbactam) should be dosed at 1.5 to 3 g IV every 6 hours, with the total sulbactam component not exceeding 4 grams per day. 1

Standard Adult Dosing Regimen

• The FDA-approved dose range is 1.5 g (1 g ampicillin/0.5 g sulbactam) to 3 g (2 g ampicillin/1 g sulbactam) administered intravenously every 6 hours 1
• Each dose should be given as a slow IV injection over at least 10-15 minutes, or diluted in 50-100 mL of compatible diluent and infused over 15-30 minutes 1
• The maximum daily sulbactam dose is 4 grams 1
• Treatment duration typically ranges from 7-14 days, though the course of IV therapy should not routinely exceed 14 days 1, 2

Pediatric Dosing (≥1 Year of Age)

• The recommended dose is 300 mg/kg/day (representing total ampicillin + sulbactam content) divided into equal doses every 6 hours via IV infusion 1
• This corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day 1
• Children weighing ≥40 kg should follow adult dosing recommendations, with sulbactam not exceeding 4 grams daily 1
• IM administration safety and efficacy have not been established in pediatric patients 1

Renal Dose Adjustments

Dosing must be reduced in renal impairment since ampicillin and sulbactam elimination kinetics are similarly affected: 1

• CrCl ≥30 mL/min: 1.5-3 g every 6-8 hours 1
• CrCl 15-29 mL/min: 1.5-3 g every 12 hours 1
• CrCl 5-14 mL/min: 1.5-3 g every 24 hours 1

Clinical Context and Appropriate Use

Unasyn is NOT recommended as first-line therapy for most skin and soft tissue infections according to current IDSA guidelines. The 2014 IDSA guidelines do not list ampicillin/sulbactam among preferred agents for uncomplicated cellulitis, purulent infections, or MRSA coverage 3. However, it may have a role in specific clinical scenarios:

When Unasyn May Be Appropriate:

• Severe infections requiring broad-spectrum coverage: For severely compromised patients (malignancy on chemotherapy, neutropenia, severe immunodeficiency, immersion injuries, animal bites), the IDSA recommends vancomycin plus either piperacillin-tazobactam or a carbapenem 3. Unasyn could serve as an alternative beta-lactam/beta-lactamase inhibitor combination in this context
• Mixed aerobic-anaerobic infections: Unasyn provides coverage against beta-lactamase producing organisms including gram-positive cocci and gram-negative bacilli 4
• Documented susceptible organisms: When culture results confirm susceptibility to ampicillin/sulbactam 2, 4

When Unasyn Should NOT Be Used:

• MRSA infections or high MRSA risk: Unasyn has no activity against MRSA 3. For purulent infections, SIRS, injection drug use, penetrating trauma, or known MRSA colonization, use vancomycin, linezolid, daptomycin, or ceftaroline instead 3
• Simple cellulitis: First-line agents include cefazolin (1 g IV every 8 hours) for MSSA or agents targeting streptococci 3

Clinical Efficacy Data

• In soft tissue infections, sulbactam/ampicillin demonstrated a 93% cure or improvement rate compared to 81% with clindamycin/tobramycin 4
• Organism eradication was achieved in 67% of cases with sulbactam/ampicillin versus 35% with clindamycin/tobramycin 4
• Sulbactam improved ampicillin sensitivity from 38% to 70% against tested isolates 4
• Overall clinical cure or improvement was 98% when IV sulbactam/ampicillin was followed by oral sultamicillin, with 100% efficacy specifically for skin and soft tissue infections 2

Important Safety Considerations

• Aminoglycoside incompatibility: If concomitant aminoglycoside therapy is needed, reconstitute and administer separately due to in vitro inactivation 1
• Adverse effects: Most commonly mild-to-moderate GI complaints and injection site pain 5, 2. Diarrhea and treatment discontinuation due to adverse events are rare 2
• Transition to oral therapy: Most patients, particularly children, should transition to oral antimicrobials following initial IV therapy 1

Critical Clinical Pitfall

The most important caveat is that Unasyn is not mentioned in the 2014 IDSA skin and soft tissue infection guidelines as a preferred agent for any category of infection 3. The guidelines specifically recommend nafcillin, cefazolin, or vancomycin-based regimens depending on MRSA risk and severity 3. Use Unasyn only when there is a specific indication for its spectrum of activity or when preferred agents cannot be used.