What is the recommended dosage for Unasyn (ampicillin and sulbactam) in patients with varying degrees of infection and renal function?

Unasyn (Ampicillin-Sulbactam) Dosage Recommendations

For standard infections in adults with normal renal function, administer Unasyn 1.5-3 g IV every 6 hours (maximum sulbactam 4 g/day), but for severe infections or multidrug-resistant organisms—particularly carbapenem-resistant Acinetobacter baumannii—use high-dose regimens of 9-12 g sulbactam daily divided every 8 hours with 4-hour extended infusions. 1, 2

Standard Adult Dosing (Normal Renal Function)

• Routine infections: 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: Do not exceed 4 grams sulbactam per day 1
• Administration: Give by slow IV injection over 10-15 minutes, or dilute in 50-100 mL compatible diluent and infuse over 15-30 minutes 1

High-Dose Regimens for Severe/Resistant Infections

For severe infections or multidrug-resistant organisms (particularly Acinetobacter baumannii with MIC ≤4 mg/L):

• Dosing: 9-12 g sulbactam daily divided into 3 doses (3-4 g every 8 hours) 2, 3
• Administration method: Use 4-hour extended infusions for each dose to optimize pharmacokinetic/pharmacodynamic properties 2, 3
• Clinical context: This high-dose approach shows comparable efficacy to imipenem for carbapenem-resistant Acinetobacter baumannii and demonstrates significantly lower nephrotoxicity than colistin (15.3% vs 33%) 2, 3

Specific Clinical Scenarios

Endocarditis (β-lactamase-producing enterococcal strains):

• Adult dose: 12 g/day IV in 4 equally divided doses (3 g every 6 hours) combined with gentamicin 3 mg/kg/day for 4-6 weeks 4, 2, 3
• Pediatric dose: 300 mg/kg/day IV in 4 equally divided doses (not to exceed adult dosing) 4

Pediatric patients ≥1 year:

• 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
• Children ≥40 kg should receive adult dosing with maximum sulbactam 4 g/day 1

Renal Impairment Dosing

Adjust frequency based on creatinine clearance (CrCl): 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

Patients on extended daily dialysis (EDD):

• Administer at least 2 g/1 g ampicillin/sulbactam twice daily, with one dose given after dialysis to avoid underdosing 5
• Standard thrice-weekly hemodialysis dosing (2 g/1 g daily) results in significant underdosing for EDD patients 6, 5

Duration of Therapy

• Standard course: Should not routinely exceed 14 days 1
• Endocarditis/deep-seated infections: May require 4-6 weeks 4, 2
• Pediatric patients: Most children transition to oral antimicrobials following initial IV therapy 1

Safety Monitoring

• Renal function: Monitor closely during high-dose therapy, particularly in patients with baseline renal impairment 3
• Nephrotoxicity advantage: Sulbactam demonstrates significantly lower nephrotoxicity rates compared to polymyxins when treating resistant infections 2, 3

Common Pitfalls to Avoid

• Underdosing resistant organisms: Doses <9 g/day sulbactam may be insufficient for severe multidrug-resistant infections, particularly carbapenem-resistant Acinetobacter baumannii 2
• Inadequate infusion time: For high-dose regimens, failing to use 4-hour extended infusions reduces efficacy and safety 2, 3
• Renal dosing errors: Patients on extended daily dialysis require higher and more frequent dosing than standard hemodialysis patients 6, 5
• Exceeding sulbactam maximum: Never exceed 4 grams sulbactam daily in standard dosing regimens 1
• Ignoring MIC values: High-dose sulbactam is most effective for isolates with MIC ≤4 mg/L; verify susceptibility before selecting therapy 2