What is the recommended dose of ampicillin (Ampicillin) sulbactam for a patient with impaired renal function or a history of penicillin allergy?

Ampicillin-Sulbactam Dosing Recommendations

Standard Dosing for Normal Renal Function

For adults with normal renal function, ampicillin-sulbactam should be dosed at 1.5-3 g (representing 1-2 g ampicillin plus 0.5-1 g sulbactam) every 6 hours IV, with a maximum sulbactam dose of 4 grams per day. 1

• The standard adult dosage ranges from 1.5 g to 3 g every 6 hours, administered by slow IV injection over 10-15 minutes or as an infusion over 15-30 minutes 1
• For severe infections such as endocarditis, the dose is 12 g/day IV divided into 4 equally divided doses (3 g every 6 hours) in combination with gentamicin 2
• Pediatric patients ≥1 year should receive 300 mg/kg/day (representing 200 mg ampicillin/100 mg sulbactam per kg/day) divided every 6 hours via IV infusion 1
• Pediatric patients weighing ≥40 kg should follow adult dosing recommendations 1

Dosing Adjustments for Renal Impairment

In patients with impaired renal function, the dosing interval must be extended based on creatinine clearance, as both ampicillin and sulbactam are primarily renally eliminated and their elimination kinetics are similarly affected. 1, 3

Renal Function-Based Dosing Algorithm:

• 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

The terminal half-life more than doubles in severe renal failure (CrCl 7-30 mL/min) compared to normal renal function, increasing from approximately 1 hour to over 9 hours 1, 3

Hemodialysis Patients:

For patients on maintenance hemodialysis, administer 1.5-3 g every 24 hours, with doses given after hemodialysis sessions. 1, 3

• Hemodialysis removes approximately 35% of ampicillin and 45% of sulbactam during a 4-hour treatment 3
• The half-life during hemodialysis is approximately 2.2-2.3 hours, compared to 13-17 hours off dialysis 3
• A slight rebound in serum concentrations occurs after hemodialysis for both drugs 3

Extended Daily Dialysis (EDD):

For critically ill patients with acute kidney injury undergoing extended daily dialysis, ampicillin-sulbactam 2 g/1 g should be administered twice daily, with one dose given after dialysis. 4

• The elimination half-life during EDD is approximately 2.8 hours for ampicillin and 3.5 hours for sulbactam 4
• Standard hemodialysis dosing (once daily) results in significant underdosing in EDD patients 5
• Dialyzer clearance is approximately 80 mL/min for ampicillin and 83 mL/min for sulbactam during EDD 4
• No significant accumulation occurs with twice-daily dosing of 2 g/1 g 4

Continuous Ambulatory Peritoneal Dialysis (CAPD):

For CAPD patients with peritonitis, administer ampicillin-sulbactam 2 g/1 g every 12 hours, either intravenously or intraperitoneally. 6

• Intraperitoneal administration provides 60% bioavailability for ampicillin and 68% for sulbactam 6
• Peak serum concentrations after intraperitoneal dosing are 48 mcg/mL for ampicillin and 27.8 mcg/mL for sulbactam 6
• Bactericidal titers remain adequate at 6 hours but not at 24 hours, necessitating twice-daily dosing 6

Penicillin Allergy Considerations

Ampicillin-sulbactam is absolutely contraindicated in patients with true penicillin allergy and should be replaced with vancomycin-based regimens. 2

• For culture-negative endocarditis in penicillin-allergic patients, use vancomycin 40 mg/kg/day IV in 2 divided doses plus gentamicin 3 mg/kg/day for 4-6 weeks 2
• For β-lactamase-producing enterococcal endocarditis in penicillin-allergic patients, use vancomycin 30 mg/kg/day IV in 2 divided doses plus gentamicin 3 mg/kg/day for 6 weeks 2
• Vancomycin is recommended only for patients unable to tolerate penicillins, as penicillin/ampicillin combinations with gentamicin are more active than vancomycin-gentamicin combinations 2

Critical Pitfalls to Avoid

• Never use standard dosing intervals in renal impairment: Failure to extend dosing intervals based on creatinine clearance leads to drug accumulation and increased toxicity risk 1, 3
• Do not underdose EDD patients: Using once-daily dosing (appropriate for conventional hemodialysis) in EDD patients results in subtherapeutic levels 5, 4
• Avoid exceeding maximum sulbactam dose: Total sulbactam should never exceed 4 grams per day regardless of indication 1
• Do not use in true penicillin allergy: Cross-reactivity with penicillins makes ampicillin-sulbactam dangerous in allergic patients 2
• Monitor for rebound after dialysis: Post-dialysis rebound in drug concentrations occurs and should be considered when timing doses 3

Duration of Therapy

• Intravenous therapy should not routinely exceed 14 days 1
• Most pediatric patients transition to oral antimicrobials following initial IV treatment 1
• For endocarditis, treatment duration is 4-6 weeks depending on valve type and clinical response 2