Ampicillin-Sulbactam IV Dosing
For moderate to severe infections with normal renal function, administer ampicillin-sulbactam 3 g (2 g ampicillin/1 g sulbactam) IV every 6 hours, with the total sulbactam dose not exceeding 4 grams per day. 1
Standard Dosing Algorithm
Normal Renal Function (CrCl ≥30 mL/min)
- Moderate infections: 1.5-3 g IV every 6 hours (standard FDA-approved dosing) 1
- Severe infections or endocarditis: 3 g IV every 6 hours (12 g/day total), administered in combination with gentamicin for endocarditis 2, 3
- Multidrug-resistant organisms (particularly Acinetobacter baumannii with MIC ≤4 mg/L): 9-12 g sulbactam per day divided into 3-4 doses, using 4-hour extended infusions to optimize pharmacokinetic/pharmacodynamic properties 2, 4
Administration Method
- Standard dosing: Administer by slow IV injection over 10-15 minutes, or as IV infusion over 15-30 minutes in 50-100 mL compatible diluent 1
- High-dose regimens for resistant organisms: Use 4-hour extended infusions to improve drug efficacy and reduce nephrotoxicity 2, 4
Renal Impairment Dosing
The ratio of ampicillin to sulbactam (2:1) remains constant regardless of renal function, as both drugs are similarly affected by renal impairment. 1, 5
Dosing by Creatinine Clearance
- 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
- Hemodialysis patients (CrCl <7 mL/min): 1.5-3 g every 24 hours, with doses administered after hemodialysis 1, 5
Hemodialysis Considerations
- Hemodialysis removes approximately 35% of ampicillin and 45% of sulbactam during a 4-hour treatment 5
- The half-life during hemodialysis decreases to 2.2-2.3 hours (from 17.4 hours for ampicillin and 13.4 hours for sulbactam off dialysis) 5
- Always dose after dialysis to avoid underdosing 5, 6
Extended Daily Dialysis (EDD)
- For patients with acute kidney injury undergoing EDD with high-flux dialyzers, use at least 2 g/1 g ampicillin-sulbactam twice daily, with one dose given after dialysis 6
- Standard hemodialysis dosing (once daily) results in significant underdosing in EDD patients due to enhanced clearance (dialyzer clearance 80-83 mL/min) 7, 6
Pediatric Dosing (≥1 Year of Age)
- Standard dose: 300 mg/kg/day (total ampicillin + sulbactam content) IV divided every 6 hours, corresponding to 200 mg ampicillin/100 mg sulbactam per kg per day 1
- Patients ≥40 kg: Use adult dosing recommendations, with maximum sulbactam dose of 4 grams per day 1
- Endocarditis: 200-300 mg/kg/day of cefoperazone component divided every 6-8 hours IV 2
Duration of Therapy
- Most serious infections: 7-10 days 4
- Severe presentations or slow clinical response: Extend to 14 days 4
- Endocarditis: 4-6 weeks depending on valve type and clinical response 3
- IV therapy should not routinely exceed 14 days 1
Safety Profile in Renal Impairment
- Ampicillin-sulbactam demonstrates significantly lower nephrotoxicity compared to colistin and polymyxins when treating multidrug-resistant infections 2, 4
- This makes it particularly advantageous for patients with borderline renal function or acute kidney injury 4
- Extended 4-hour infusions further reduce nephrotoxicity risk compared to bolus dosing 4
Critical Pitfalls to Avoid
- Underdosing in severe infections: Standard doses (1.5 g every 6 hours) may be insufficient for resistant organisms or severe presentations; consider high-dose regimens (9-12 g sulbactam/day) for multidrug-resistant Acinetobacter baumannii 2, 4
- Incorrect dosing in extended daily dialysis: Do not use standard hemodialysis dosing (once daily) for EDD patients, as this results in significant underdosing 7, 6
- Dosing before dialysis: Always administer doses after hemodialysis to prevent subtherapeutic levels 5, 6
- Exceeding maximum sulbactam dose: Total sulbactam should not exceed 4 grams per day in standard dosing regimens 1