What is the recommended dosing for Unasyn (Ampicillin/Sulbactam) for soft tissue infections?

Unasyn Dosing for Soft Tissue Infections

Primary Recommendation

For soft tissue infections, Unasyn (ampicillin/sulbactam) is dosed at 1.5-3 g (1-2 g ampicillin plus 0.5-1 g sulbactam) intravenously every 6 hours in adults, with a maximum sulbactam dose of 4 grams per day, though it is not a first-line agent according to IDSA guidelines. 1

Critical Context Before Prescribing

• The IDSA does not recommend Unasyn as first-line therapy for most skin and soft tissue infections. 2
• Unasyn has no activity against MRSA and should not be used when MRSA is suspected or in high-risk populations. 2
• For simple cellulitis, cefazolin (for MSSA) or agents targeting streptococci are preferred over Unasyn. 2
• Unasyn may serve as an alternative beta-lactam/beta-lactamase inhibitor combination for severely compromised patients when vancomycin plus piperacillin-tazobactam or a carbapenem is recommended. 2

Standard Adult Dosing

Intravenous Administration:

• 1.5 g to 3 g (1-2 g ampicillin/0.5-1 g sulbactam) every 6 hours 1
• Maximum sulbactam dose: 4 grams per day 1
• Concentrations between 3 and 45 mg/mL (2-30 mg ampicillin/1-15 mg sulbactam/mL) are recommended for IV use 1
• Clinical studies used 1 g sulbactam per 2 g ampicillin every 6 hours with a 93% cure rate in soft tissue infections 3

Pediatric Dosing (≥1 Year)

• 300 mg/kg/day total (200 mg ampicillin/100 mg sulbactam per kg/day) divided every 6 hours via IV infusion 1
• Pediatric patients ≥40 kg should follow adult dosing recommendations 1
• Maximum sulbactam dose: 4 grams per day 1
• IV therapy should not routinely exceed 14 days 1

Renal Impairment Adjustments

Dosing must be reduced based on creatinine clearance: 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

Treatment Duration and Monitoring

• Course of IV therapy should not routinely exceed 14 days 1
• Most pediatric patients transitioned to oral antimicrobials following initial IV treatment 1
• Mean treatment duration in neonatal studies was 7.4 days (range 4-14 days) with significant resolution within 48 hours 4
• Clinical studies in adults used 7-10 day courses 5

Clinical Efficacy Data

• Ampicillin/sulbactam demonstrated 93% cure or improvement rate versus 81% with clindamycin/tobramycin in soft tissue infections 3
• Organism eradication was superior: 67% versus 35% compared to clindamycin/tobramycin 3
• Sulbactam addition improved ampicillin sensitivity from 38% to 70% against mixed bacterial isolates 3
• Effective against beta-lactamase producing organisms (88% beta-lactamase production rate in one study) with 93.8% bacteriologic cure rate 4

Important Clinical Pitfalls

• Do not use for MRSA infections or when MRSA risk is high—use vancomycin, linezolid, daptomycin, or ceftaroline instead 2
• Aminoglycosides must be reconstituted and administered separately due to in vitro inactivation by aminopenicillins 1
• Pain at injection site is the most commonly reported adverse effect 5
• Solutions must be used within specific timeframes after reconstitution (2-8 hours at room temperature depending on concentration and diluent) 1