What is the recommended dosage and frequency of Ampicillin (Ampicillin Sulbactam) in patients with Chronic Kidney Disease (CKD)?

Ampicillin-Sulbactam Dosing in Chronic Kidney Disease

In patients with CKD, ampicillin-sulbactam dosing must be reduced based on creatinine clearance, with the standard dose of 1.5-3g every 6-8 hours adjusted to every 12 hours for moderate impairment (CrCl 15-29 mL/min) and every 24 hours for severe impairment (CrCl 5-14 mL/min). 1

Standard Dosing in Normal Renal Function

• The recommended adult dose is 1.5g to 3g every 6 hours (representing 1g ampicillin/0.5g sulbactam to 2g ampicillin/1g sulbactam) 1
• Total sulbactam should not exceed 4 grams per day 1
• Can be administered IV over 10-15 minutes or as infusion over 15-30 minutes 1

Dose Adjustments Based on Creatinine Clearance

The FDA label provides clear guidance for renal dose adjustments 1:

CrCl ≥30 mL/min

• Dose: 1.5-3g every 6-8 hours (no adjustment needed) 1

CrCl 15-29 mL/min (Moderate Impairment)

• Dose: 1.5-3g every 12 hours 1
• Half-life increases to approximately 5 hours 1

CrCl 5-14 mL/min (Severe Impairment)

• Dose: 1.5-3g every 24 hours 1
• Half-life increases to approximately 9 hours 1

Pharmacokinetic Rationale

• Both ampicillin and sulbactam are primarily renally eliminated (approximately 71% and 78%, respectively) 2
• The elimination kinetics of both drugs are similarly affected by renal impairment, maintaining a constant ratio regardless of renal function 1, 3
• Terminal half-life more than doubles in severe renal failure compared to normal function 3
• Creatinine clearance significantly correlates with total body clearance for both ampicillin (r=0.88) and sulbactam (r=0.54) 3

Special Considerations for Dialysis Patients

Hemodialysis (Intermittent)

• Dose: 1.5-3g every 24 hours, administered AFTER dialysis 1, 3
• Hemodialysis removes approximately 35% of ampicillin and 45% of sulbactam during a 4-hour treatment 3
• Half-life during dialysis decreases to 2.2-2.3 hours, but increases to 13-17 hours between sessions 3
• A slight rebound in serum concentrations occurs after dialysis 3

Extended Daily Dialysis (EDD)

• Dose: At least 2g/1g (ampicillin/sulbactam) twice daily, with one dose after dialysis 2
• Standard hemodialysis dosing (once daily) results in significant underdosing in EDD patients 4
• Dialyzer clearance is substantially higher (80-83 mL/min) with high-flux membranes 2
• Half-life during EDD is only 1.5-3.5 hours, necessitating more frequent dosing 4, 2

Important Clinical Caveats

• Calculate creatinine clearance using the Cockcroft-Gault formula when only serum creatinine is available 1
• The serum creatinine should represent steady-state renal function 1
• Avoid nephrotoxic drug combinations in advanced CKD to prevent further kidney damage 5
• Population pharmacokinetic modeling confirms that creatinine clearance reduces inter-individual variability in clearance by 16% 6
• The recommended dose adjustments maintain adequate time above MIC (>50% of treatment period) for most pathogens 6

Monitoring Recommendations

• Reassess renal function regularly, as changes in kidney function require dose adjustments 7
• Drug dosing errors are common in renal impairment and can cause adverse effects 7
• Consider consulting nephrology for complex cases, particularly those on renal replacement therapy 5