What is the appropriate dosing of Amikacin (an aminoglycoside antibiotic) for Urinary Tract Infection (UTI)?

From the Guidelines

For the treatment of urinary tract infections (UTIs), a single dose of amikacin is recommended, as it has been shown to be effective in achieving high microbiologic cure rates of 87-100%. This approach is supported by a meta-analysis of 13 studies including 13,804 patients, which found that a single-dose of aminoglycoside was effective in the treatment of lower urinary tract infections 1. The use of a single dose is also beneficial due to the high concentration of aminoglycosides in the urine, which remains above the therapeutic level for days after administration.

Key considerations for the use of amikacin in UTIs include:

• Aminoglycosides are excreted in the active form primarily by the renal route, with a concentration exceeding peak plasma levels by 25- to 100-fold 1
• Amikacin has maintained excellent activity against the majority of uropathogens, including CRE, with clinical isolates of CRE in Taiwan reporting amikacin as the most susceptible agent (38.2%) 1
• However, there is currently insufficient evidence to support the use of single-dose aminoglycoside for patients with complicated UTI (cUTI) due to CRE 1

In terms of dosing, while the exact dose is not specified in the provided evidence, a single dose of amikacin is recommended, with the dose likely to be in the range of 15 mg/kg. It is essential to note that dosage adjustments are necessary for patients with renal impairment, and therapeutic drug monitoring is crucial to prevent toxicity. Potential side effects of amikacin include nephrotoxicity and ototoxicity, so monitoring renal function and hearing is vital during treatment.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION: ... When amikacin is indicated in uncomplicated urinary tract infections, a dose of 250 mg twice daily may be used. The appropriate dosing of Amikacin for Urinary Tract Infection (UTI) is:

• 250 mg twice daily for uncomplicated infections 2 Key points:
• This dosage is for patients with normal renal function
• Serum amikacin concentrations should be measured to assure adequate but not excessive levels
• Dosage should be adjusted based on renal function and serum concentrations 2

From the Research

Amikacin Dosing for Urinary Tract Infection (UTI)

• The appropriate dosing of Amikacin for UTI can vary depending on the severity of the infection and the patient's renal function.
• A study from 1986 3 found that a single dose of Amikacin (single-shot) was effective in treating uncomplicated UTIs, with a positive response in 73.7% of patients.
• Another study from 2014 4 found that the dosage of Amikacin should be dependent on the stage of chronic kidney disease (CKD), with patients in stage 3A CKD receiving 7.5 mg/kg/day, and those in stage 4 CKD receiving 4 mg/kg/day or 6.0 mg/kg every two days.
• A study from 1993 5 compared once-daily and twice-daily dosing regimens of Amikacin, and found that both regimens were effective and safe in treating systemic Gram-negative infections.
• A study from 1977 6 compared low and high dosage regimens of Amikacin in the treatment of complicated UTIs, and found that the low dosage regimen (7.5 mg/Kg) was satisfactory and had fewer adverse effects.
• Another study from 1979 7 found that Amikacin was highly effective in treating chronic pyelonephritis and cystitis, and did not cause any permanent nephrotoxic or ototoxic damage.

Dosage Regimens

• Single-shot dosing: 73.7% positive response in uncomplicated UTIs 3
• Once-daily dosing: effective and safe in treating systemic Gram-negative infections 5
• Twice-daily dosing: effective and safe in treating systemic Gram-negative infections 5
• Low dosage regimen (7.5 mg/Kg): satisfactory in treating complicated UTIs, with fewer adverse effects 6
• Dosage dependent on CKD stage:
  • Stage 3A CKD: 7.5 mg/kg/day 4
  • Stage 4 CKD: 4 mg/kg/day or 6.0 mg/kg every two days 4