What is the recommended dose of Unasyn (Ampicillin-Sulbactam) for a patient?

Unasyn (Ampicillin-Sulbactam) Dosing Recommendations

For adults, the standard dose of Unasyn is 1.5 to 3 grams IV every 6 hours, with the total sulbactam component not exceeding 4 grams per day. 1

Adult Dosing

• Standard regimen: 1.5 g (1 g ampicillin/0.5 g sulbactam) to 3 g (2 g ampicillin/1 g sulbactam) IV every 6 hours 1
• Maximum sulbactam dose: 4 grams per day 1
• Administration: Slow IV injection over 10-15 minutes, or diluted in 50-100 mL compatible diluent as IV infusion over 15-30 minutes 1

For specific indications, the FDA label provides clear guidance that this dosing range applies broadly to infections where Unasyn is indicated. 1

Pediatric Dosing (≥1 Year of Age)

• Standard dose: 300 mg/kg/day (total ampicillin + sulbactam content) divided every 6 hours via IV infusion 1
• This corresponds to 200 mg ampicillin/100 mg sulbactam per kg per day 1
• For children ≥40 kg: Use adult dosing recommendations, with maximum sulbactam of 4 grams per day 1
• Duration: IV therapy should not routinely exceed 14 days 1

The American Heart Association guidelines for endocarditis specify 12 g/day IV in 4 equally divided doses (3 g every 6 hours) for adults, which aligns with the upper end of FDA dosing. 2 For pediatric endocarditis, they recommend 300 mg/kg/day IV in 4-6 equally divided doses. 2

Renal Impairment Dosing

Dosing must be adjusted based on creatinine clearance, as both ampicillin and sulbactam are renally eliminated: 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

Critical caveat: Patients on extended daily dialysis may require higher or more frequent dosing than standard hemodialysis patients, as elimination half-life can be as short as 1.5 hours during dialysis, risking significant underdosing with standard renal failure regimens. 3 For CAPD patients, dosing every 12 hours is recommended. 4

Indication-Specific Dosing from Guidelines

For HACEK endocarditis (native or prosthetic valve):

• Adult: 12 g/24 hours IV in 4 equally divided doses (3 g every 6 hours) for 4 weeks (native valve) or 6 weeks (prosthetic valve) 2
• Pediatric: 300 mg/kg/24 hours IV divided into 4 or 6 equally divided doses 2

For culture-negative endocarditis (native valve):

• Adult: 12 g/day IV in 4 equally divided doses for 4-6 weeks, combined with gentamicin 2
• Pediatric: 300 mg/kg/day IV in 4-6 equally divided doses for 4-6 weeks 2

For intra-abdominal infections (non-critically ill):

• Amoxicillin-clavulanate 1.2-2.2 g every 6 hours is listed as an option, though this is the oral formulation 2
• For complicated pediatric intra-abdominal infections, 200 mg/kg/day of ampicillin-sulbactam given every 6 hours is recommended 5

Important Clinical Considerations

• Neonates and infants <1 year: Safety and efficacy not established by FDA for IV Unasyn; pediatric infectious disease consultation recommended 1, 5
• IM administration: May be given by deep IM injection in adults, but safety/efficacy not established for IM use in pediatric patients 1
• Peak levels: Achieved in 15 minutes to 1 hour after 15-minute IV infusion 6
• Oral transition: Most pediatric patients in clinical trials transitioned to oral antimicrobials after initial IV therapy 1

The key distinction is that IV Unasyn dosing (1.5-3 g every 6 hours for adults) should not be confused with oral formulations, which have different pharmacokinetics and dosing schedules. 5