How should aztreonam be dosed in a patient with end‑stage renal disease (CKD stage 5) and serum creatinine 4.75 mg/dL, including adjustments for intermittent hemodialysis?

Aztreonam Dosing in CKD Stage 5 (Creatinine 4.75 mg/dL)

For a patient with CKD stage 5 and creatinine 4.75 mg/dL, administer aztreonam as a standard loading dose of 1-2 g initially, followed by one-fourth of the usual maintenance dose at the standard interval (every 6,8, or 12 hours depending on infection severity). 1

Dose Adjustment Algorithm

Step 1: Estimate Creatinine Clearance

• With a creatinine of 4.75 mg/dL in CKD stage 5, the estimated creatinine clearance is likely <10 mL/min/1.73 m² 1
• Use the Cockcroft-Gault formula if needed: For males: [weight (kg) × (140−age)] / [72 × serum creatinine (mg/dL)]; for females multiply by 0.85 1

Step 2: Loading Dose (First Dose)

• Give the full usual initial dose: 500 mg, 1 g, or 2 g depending on infection severity 1
• For severe systemic or life-threatening infections: 2 g loading dose 1
• For moderately severe infections: 1 g loading dose 1
• For urinary tract infections: 500 mg or 1 g loading dose 1

Step 3: Maintenance Dosing for CrCl <10 mL/min

• Reduce maintenance dose to one-fourth (25%) of the usual initial dose 1
• Maintain the standard dosing interval (6,8, or 12 hours) 1
• Example: If loading dose was 2 g, give 500 mg every 6-8 hours as maintenance 1

Step 4: If Patient is on Hemodialysis

• Give the standard loading dose initially 1, 2
• Maintenance: one-fourth of the initial dose at usual intervals 1
• Supplemental dose after each hemodialysis session: one-eighth of the initial dose 1
• Hemodialysis removes 27-58% of aztreonam over 4 hours, with dialysis clearance of 36.6-43.2 mL/min 2
• Alternative recommendation: give half the usual maintenance dose after each dialysis 2

Step 5: If Patient is on Peritoneal Dialysis

• For CAPD patients: 1 g IV loading dose, followed by 0.5 g intraperitoneally every 6 hours for peritonitis 2
• Peritoneal dialysis clearance is only 2.1 mL/min, removing approximately 9.7% of the dose 2

Key Pharmacokinetic Considerations

Aztreonam elimination is highly dependent on renal function:

• In patients with normal renal function, aztreonam clearance correlates strongly with creatinine clearance (r² = 0.90, mean CL/CrCl ratio = 1.11) 3
• Half-life increases from 1.6-2 hours in normal renal function to 7-9 hours in severe renal impairment 3, 2
• In hemodialysis patients, half-life is 7.9 hours interdialytically and 2.7 hours during dialysis 2

Volume of distribution remains stable:

• Mean steady-state volume of distribution is 0.16 L/kg, approximating extracellular fluid volume 3
• This parameter is not significantly affected by renal impairment 3

Critical Pitfalls to Avoid

Do not give full maintenance doses without adjustment:

• Failure to reduce maintenance doses in severe renal impairment leads to drug accumulation and potential toxicity 1, 4
• The metabolite SQ 26,992 accumulates progressively in renal failure (trough levels increased from 2.6 to 38.2 mcg/mL over 7 days in one hemodialysis patient) 5

Do not skip the loading dose:

• Always give the full loading dose regardless of renal function to achieve therapeutic levels quickly 1, 6
• Population pharmacokinetic modeling supports this approach with >90% probability of target attainment 6

Monitor for accumulation in elderly patients:

• Serum creatinine may not accurately reflect renal function in elderly patients due to decreased muscle mass 1
• Creatinine clearance estimation is essential, not just serum creatinine alone 1, 4

Monitoring During Therapy

• Reassess renal function every 2-3 days as kidney function may change during treatment 7
• Aztreonam clearance can increase during therapy as renal function improves 3
• Continue therapy for at least 48 hours after clinical improvement or bacterial eradication 1