What is the appropriate Unasyn (ampicillin‑sulbactam) dosing for an adult with a multidrug‑resistant infection based on estimated glomerular filtration rate?

Unasyn (Ampicillin-Sulbactam) Dosing in Renal Impairment for MDR Infections

For adults with multidrug-resistant infections and impaired renal function, dose Unasyn based on creatinine clearance: 1.5–3 g every 6–8 hours for CrCl ≥30 mL/min, every 12 hours for CrCl 15–29 mL/min, and every 24 hours for CrCl 5–14 mL/min, with post-dialysis dosing for hemodialysis patients. 1

Standard Dosing for Normal Renal Function

• The recommended adult dose is 1.5 g (1 g ampicillin/0.5 g sulbactam) to 3 g (2 g ampicillin/1 g sulbactam) every 6 hours, with total sulbactam not exceeding 4 grams daily. 1
• Administer by slow IV injection over 10–15 minutes or as an infusion over 15–30 minutes in 50–100 mL compatible diluent. 1

Renal Dose Adjustments by Creatinine Clearance

The FDA-approved dosing table provides clear guidance based on measured creatinine clearance:

CrCl ≥30 mL/min/1.73m²

• Dose: 1.5–3 g every 6–8 hours 1
• No significant adjustment needed; both ampicillin and sulbactam elimination kinetics remain relatively preserved. 2

CrCl 15–29 mL/min/1.73m²

• Dose: 1.5–3 g every 12 hours 1
• Terminal half-life more than doubles compared to normal renal function, necessitating extended dosing intervals. 2

CrCl 5–14 mL/min/1.73m²

• Dose: 1.5–3 g every 24 hours 1
• Severe renal impairment significantly prolongs drug elimination (half-life increases from 1 hour to up to 24 hours). 2

Hemodialysis Patients (CrCl <5 mL/min)

• Dose: 1.5–3 g every 24 hours, administered after dialysis on dialysis days 1, 2
• Hemodialysis removes approximately 35% of ampicillin and 45% of sulbactam over 4 hours, with half-lives during dialysis dropping to 2.2–2.3 hours. 2
• A slight rebound in serum concentrations occurs post-dialysis, but supplemental dosing after the session is still required. 2

Critical Considerations for Accurate Dosing

Calculate Actual Creatinine Clearance—Don't Rely on Serum Creatinine Alone

• Use the Cockcroft-Gault formula to convert serum creatinine to creatinine clearance, accounting for age, weight, and sex. 1
  • Males: CrCl = [weight (kg) × (140 − age)] / (72 × serum creatinine)
  • Females: CrCl = 0.85 × male value 1
• Serum creatinine alone is unreliable in elderly or critically ill patients with reduced muscle mass and may lead to significant overdosing. 3, 4

De-Index eGFR for Drug Dosing

• Laboratory-reported eGFR is indexed to body surface area (mL/min/1.73m²); for drug dosing, calculate non-indexed eGFR (mL/min) by multiplying by the patient's BSA/1.73. 3
• Failure to de-index can result in inappropriate dose selection, particularly in patients with extremes of body size. 3

Reassess Renal Function Regularly in Critically Ill Patients

• Creatinine clearance should be recalculated using urine output formula (U × V / P) at therapy initiation and whenever clinical status changes. 5
• Dynamic renal function in acute kidney injury or sepsis can rapidly alter drug clearance, risking underdosing in patients on extended daily dialysis (half-life may drop to 1.5 hours). 6

Special Populations and MDR Infections

Patients with MDR Organisms and Renal Impairment

• Renal dysfunction (eGFR 30–59 mL/min/1.73m²) increases the odds of MDR infections by 19%, and eGFR <30 mL/min/1.73m² by 41%. 7
• Higher baseline infection risk in this population underscores the importance of adequate dosing to achieve bactericidal concentrations while avoiding toxicity. 7

Extended Daily Dialysis (EDD)

• Standard hemodialysis dosing (every 24 hours) may result in significant underdosing in EDD patients due to enhanced drug clearance (half-life ~1.5 hours on EDD vs. 17.4 hours off standard HD). 6
• Consider more frequent dosing (e.g., every 12 hours) or therapeutic drug monitoring if available for EDD patients with severe infections. 6

Pediatric Dosing Adjustments

• For children ≥1 year: 300 mg/kg/day (total ampicillin + sulbactam content) divided every 6 hours via IV infusion. 1
• Children ≥40 kg should follow adult dosing with renal adjustments as above; total sulbactam should not exceed 4 grams daily. 1

Common Pitfalls to Avoid

• Do not dose based on "normal" serum creatinine in elderly or sarcopenic patients—always calculate CrCl to prevent overdosing. 3, 4
• Do not forget to administer post-dialysis doses—both drugs are significantly dialyzed and require replacement. 2
• Do not use indexed eGFR directly from lab reports for dosing decisions—convert to non-indexed values first. 3
• Do not assume stable renal function in critically ill patients—reassess frequently, especially in sepsis or acute kidney injury. 5, 6