What is the appropriate dosing of Amikacin (an aminoglycoside antibiotic) for a patient with a complicated Urinary Tract Infection (UTI) and potentially Impaired Renal Function?

From the Guidelines

For a patient with a complicated Urinary Tract Infection (UTI) and potentially Impaired Renal Function, the appropriate dosing of Amikacin is 15 mg/kg/day IV QD, with adjustments made based on creatinine clearance and therapeutic drug monitoring to minimize the risk of nephrotoxicity and ototoxicity. The dosing of Amikacin should be individualized, taking into account the patient's renal function, as indicated by studies such as 1.

Key Considerations

• The dose of Amikacin should be adjusted for patients with renal impairment, with a recommended dose of 15 mg/kg/day IV QD, as stated in 1.
• Therapeutic drug monitoring is essential to avoid toxicity, with peak levels drawn 30 minutes after infusion and trough levels just before the next dose.
• Amikacin should be administered intravenously over 30-60 minutes.
• Potential toxicities include nephrotoxicity and ototoxicity, so baseline and periodic assessment of renal function, hearing, and vestibular function is recommended.
• Adequate hydration should be maintained throughout treatment to minimize kidney damage.

Treatment Duration

• The treatment duration for complicated UTIs is generally 5-7 days, as recommended in 1.
• The duration of treatment should be individualized according to the infection site, source control, underlying comorbidities, and initial response to therapy.

Monitoring and Adjustments

• Serum drug concentrations should be monitored to avoid toxicity, as indicated in 1 and 1.
• Dosing adjustments should be made based on creatinine clearance and therapeutic drug monitoring to minimize the risk of nephrotoxicity and ototoxicity.

From the FDA Drug Label

Intramuscular Administration for Patients with Impaired Renal Function Whenever possible, serum amikacin concentrations should be monitored by appropriate assay procedures. Doses may be adjusted in patients with impaired renal function either by administering normal doses at prolonged intervals or by administrating reduced doses at a fixed interval

Normal Dosage at Prolonged Intervals If the creatinine clearance rate is not available and the patient's condition is stable, a dosage interval in hours for the normal dose can be calculated by multiplying the patient's serum creatinine by 9, e.g., if the serum creatinine concentration is 2 mg/100 mL, the recommended single dose (7. 5 mg/kg) should be administered every 18 hours.

Reduced Dosage at Fixed Time Intervals When renal function is impaired and it is desirable to administer amikacin at a fixed time interval, dosage must be reduced. In these patients, serum amikacin concentrations should be measured to assure accurate administration of amikacin and to avoid concentrations above 35 mcg/mL

For a patient with a complicated Urinary Tract Infection (UTI) and potentially Impaired Renal Function, the appropriate dosing of Amikacin should be determined by one of two methods:

• Normal Dosage at Prolonged Intervals: Calculate the dosage interval in hours for the normal dose by multiplying the patient's serum creatinine by 9.
• Reduced Dosage at Fixed Time Intervals: Reduce the dosage in proportion to the reduction in the patient's creatinine clearance rate, using the formula: Maintenance Dose = observed CC in mL/minX Calculated loading dose in mg Every 12 Hours normal CC in mL/min It is essential to monitor serum amikacin concentrations and renal function to avoid toxicity and ensure effective treatment 2.

From the Research

Dosing of Amikacin for Complicated UTI with Impaired Renal Function

• The appropriate dosing of Amikacin for a patient with a complicated Urinary Tract Infection (UTI) and potentially impaired renal function is crucial to ensure effective treatment and minimize the risk of nephrotoxicity.
• A study from 1976 3 administered Amikacin (250 mg four times daily for 10 days) to 22 patients with long-standing, severe infections of the urinary tract, and found that therapy with Amikacin was completely successful in 14 patients.
• The same study 3 also indicated that the half-life of Amikacin may be increased five- to 10-fold in patients with renal insufficiency, and a tentative dosage schedule was prepared for patients with various degrees of impaired renal function.
• A more recent study from 2020 4 found that the Cmax/MIC ratio can be used to predict the time required for a clinical cure, and that Ctrough can be used to predict the occurrence of nephrotoxicity in patients receiving Amikacin therapy.
• Another study from 2014 5 used a dose of 15 mg/kg/day for 10 days and found a clinical success rate of 97.2% and an overall bacteriological success rate of 91.7% on the 3rd day of treatment.
• A study from 1977 6 compared the recommended dose of Amikacin sulfate (15 mg./Kg.) with a lower dose (7.5 mg./Kg.) and found that low dosage Amikacin sulfate is satisfactory in the treatment of complicated urinary tract infections.
• In terms of nephrotoxicity, a study from 2019 7 found that the incidence of Amikacin-induced nephrotoxicity was lower than that reported in previous studies, and that therapeutic drug monitoring (TDM) may not be necessary in patients with normal kidney function.

Key Considerations

• The dose of Amikacin should be adjusted based on the patient's renal function, with a tentative dosage schedule prepared for patients with various degrees of impaired renal function 3.
• The Cmax/MIC ratio and Ctrough can be used to predict the time required for a clinical cure and the occurrence of nephrotoxicity, respectively 4.
• A dose of 15 mg/kg/day for 10 days has been shown to be effective in treating complicated UTIs 5.
• Low dosage Amikacin sulfate may be satisfactory in the treatment of complicated urinary tract infections 6.
• Therapeutic drug monitoring (TDM) may not be necessary in patients with normal kidney function, but initial monitoring for kidney function in clinical laboratories may be useful 7.