Ampicillin-Sulbactam (Unasyn) Dosing for Multidrug-Resistant Infections in CKD Patients
For patients with chronic kidney disease and multidrug-resistant infections, ampicillin-sulbactam dosing must be adjusted based on creatinine clearance, with the standard dose of 1.5-3 g every 6-8 hours reduced to every 12 hours for CrCl 15-29 mL/min and every 24 hours for CrCl 5-14 mL/min, not to exceed 4 grams of sulbactam daily. 1
Standard Dosing in 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 via slow IV injection over 10-15 minutes or IV infusion over 15-30 minutes 1
- For severe multidrug-resistant infections, particularly Acinetobacter baumannii, higher doses of 9-12 g/day of sulbactam component (corresponding to 18-24 g/day total ampicillin-sulbactam) in 3 divided doses are recommended 2
- The total sulbactam dose should not exceed 4 grams per day in standard dosing 1
Renal Dose Adjustments
The FDA-approved dosing adjustments based on creatinine clearance are:
- 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
Pharmacokinetic Rationale
- Both ampicillin and sulbactam are eliminated primarily by the kidneys (approximately 71% and 78%, respectively), and their elimination kinetics are similarly affected by renal impairment 3, 4
- The half-life increases from approximately 1 hour in normal renal function to over 17 hours in end-stage renal disease 3, 5
- The ratio of ampicillin to sulbactam remains constant regardless of renal function, so the fixed combination can be adjusted proportionally 3, 5
Hemodialysis Patients
For patients on maintenance hemodialysis:
- Administer 1.5-3 g every 24 hours, with dosing given after hemodialysis on dialysis days 1, 3
- Hemodialysis removes approximately 35% of ampicillin and 45% of sulbactam during a 4-hour treatment 3
- The half-life during hemodialysis decreases to approximately 2.2-2.3 hours for both drugs 3
Extended Daily Dialysis Considerations
- For critically ill patients with acute kidney injury undergoing extended daily dialysis (8-hour sessions), a twice-daily dosing schedule of at least 2 g/1 g ampicillin-sulbactam is required to avoid underdosing 6, 4
- One dose should be administered after dialysis 4
- Standard hemodialysis dosing (once daily) results in significant underdosing in extended dialysis due to enhanced clearance 6
Continuous Renal Replacement Therapy (CRRT)
- For critically ill patients receiving CRRT, standard dosing recommendations for intermittent hemodialysis cannot be directly applied 7
- Antibiotic pharmacokinetics differ significantly in CRRT compared to normal renal function or intermittent hemodialysis 7
- Consultation with infectious diseases and nephrology specialists is recommended for optimal dosing in CRRT patients 7
Critical Considerations for Multidrug-Resistant Organisms
For MDR Acinetobacter baumannii infections specifically:
- Sulbactam has intrinsic activity against Acinetobacter species at MIC ≤4 mg/L 2
- Higher doses (9-12 g/day of sulbactam component) are recommended for severe infections in patients with normal renal function 2
- In CKD patients with MDR infections, proportional dose reduction based on creatinine clearance should be applied to these higher doses while maintaining therapeutic levels 2
Important Caveats
- β-lactamase-producing strains: Ampicillin-sulbactam is effective against β-lactamase-producing enterococci, with 6 weeks of therapy recommended for endocarditis 2
- Monitoring: Assess clinical response within 48-72 hours and reassess renal function every 2-3 days to adjust dosing as renal function changes during treatment 8
- Avoid underdosing: In critically ill patients with changing renal function or those on renal replacement therapy, err on the side of adequate dosing rather than excessive dose reduction, as underdosing increases mortality risk with MDR infections 6, 4