Is single-dose amikacin (an aminoglycoside antibiotic) suitable for treating urinary tract infections (UTIs) in patients with end-stage renal disease (ESRD)?

Single-Dose Amikacin for UTI in ESRD Patients

Single-dose amikacin is not recommended for treating UTIs in patients with end-stage renal disease (ESRD) due to significant risks of toxicity and altered pharmacokinetics requiring careful dosage adjustment and monitoring. 1

Amikacin Dosing in ESRD

Pharmacokinetic Considerations

• Amikacin clearance is almost exclusively renal, requiring significant dosage adjustments in ESRD patients 2
• The half-life of amikacin may be increased 5-10 fold in patients with renal insufficiency, leading to potential drug accumulation and toxicity 3
• In ESRD patients on hemodialysis, the mean serum half-life of amikacin is approximately 28 hours when not on dialysis, compared to 3.75 hours during hemodialysis 4

Recommended Dosing Approach

• For ESRD patients, the dosing frequency should be reduced to two or three times per week, but the dose should be maintained at 12-15 mg/kg to ensure concentration-dependent bactericidal effect 2
• Smaller doses may reduce efficacy, making single-dose therapy inadequate for treating UTIs in ESRD 2, 1
• Administration should occur after dialysis to facilitate directly observed therapy and prevent premature removal of the drug 2

Monitoring Requirements

• Serum drug concentration measurements are essential in ESRD patients to avoid toxicity 1, 4
• Target peak concentrations should be below 35 μg/mL and trough concentrations below 10 μg/mL 1
• Baseline and regular monitoring should include 2:
  • Audiogram and vestibular testing
  • Serum creatinine measurement
  • Regular assessment of renal function
  • Monitoring for auditory or vestibular symptoms

Toxicity Concerns

• Nephrotoxicity: Amikacin may cause renal impairment in 8.7% of patients, with higher frequency in those with initially increased creatinine levels 2
• Ototoxicity: High-frequency hearing loss occurs in up to 24% of patients receiving amikacin, with higher rates in those receiving higher doses 2
• Risk of toxicity increases with 2:
  • Concurrent use of diuretics
  • Larger total cumulative doses
  • Use of other nephrotoxic agents

Alternative Approaches

• For ESRD patients with UTIs, modified dosing regimens have shown efficacy:
  • Patients on hemodialysis may receive 5 mg/kg every two days 5
  • Patients on peritoneal dialysis may receive 4 mg/kg every two days 5
  • Lower doses (7.5 mg/kg) have shown efficacy in complicated UTIs in patients with normal renal function, but must be adjusted for ESRD 6, 7

Clinical Pitfalls to Avoid

• Administering standard doses without adjustment for renal function can lead to dangerous drug accumulation 4
• Using single-dose therapy in ESRD patients may result in subtherapeutic levels and treatment failure 5
• Failing to monitor drug levels may result in toxicity, as serum half-life varies significantly between patients 3, 4
• Administering amikacin before dialysis will result in premature removal of the drug and potential treatment failure 2