How should gentamicin be used to minimize the risk of renal injury?

From the Guidelines

To minimize the risk of renal injury when using gentamicin, administer it in daily multiple divided doses rather than a single daily dose, with a total dose of approximately 3 mg·kg−1·d−1, and adjust the dose to achieve a 1-hour serum concentration of approximately 3 μg/mL and a trough concentration of <1 μg/mL, as recommended by the American Heart Association 1.

Key Considerations

• Gentamicin should be administered every 8 hours to patients with normal renal function, with dose adjustments as needed to achieve target serum concentrations 1.
• Regular monitoring of renal function through serum creatinine and estimated glomerular filtration rate (eGFR) should be performed before starting therapy and at least twice weekly during treatment.
• Limit the duration of therapy to the shortest course possible, as longer courses significantly increase nephrotoxicity risk.
• Ensure adequate hydration throughout treatment and avoid concurrent nephrotoxic medications such as NSAIDs, ACE inhibitors, and other aminoglycosides.

Patient-Specific Factors

• Patients with pre-existing renal impairment, advanced age, or dehydration require dose adjustments and more frequent monitoring.
• Gentamicin causes renal injury through accumulation in proximal tubular cells, leading to cell death and decreased filtration capacity, which is why maintaining appropriate drug levels and limiting exposure time are critical protective strategies.

Additional Guidance

• The European Society of Cardiology recommends gentamicin can be given in a single daily dose in order to reduce renal toxicity, but this is not universally agreed upon, and the American Heart Association recommends multiple daily doses 1.
• It is essential to weigh the benefits and risks of gentamicin use in each patient, considering the potential for renal injury and the need for effective antimicrobial therapy.

From the FDA Drug Label

PATIENTS WITH IMPAIRED RENAL FUNCTION Dosage must be adjusted in patients with impaired renal function to assure therapeutically adequate, but not excessive blood levels Whenever possible serum concentration of gentamicin should be monitored. One method of dosage adjustment is to increase the interval between administration of the usual doses. Since the serum creatinine concentration has a high correlation with the serum half-life of gentamicin, this laboratory test may provide guidance for adjustment of the interval between doses The interval between doses (in hours) may be approximated by multiplying the serum creatinine level (mg/100 mL) by 8.

To minimize the risk of renal injury when using gentamicin, the following guidelines should be followed:

• Dosage adjustment is necessary in patients with impaired renal function to ensure therapeutic levels are achieved without excessive blood levels.
• Serum concentration monitoring of gentamicin is recommended whenever possible.
• The interval between doses can be adjusted based on the serum creatinine level, with the interval in hours approximated by multiplying the serum creatinine level (mg/100 mL) by 8.
• In patients with serious systemic infections and renal impairment, it may be desirable to administer gentamicin more frequently but in reduced doses, with serum concentrations measured to ensure adequate but not excessive levels.
• The status of renal function should be closely monitored, as deteriorating renal function may require a greater reduction in dosage than specified in guidelines for patients with stable renal impairment 2.

From the Research

Gentamicin and Renal Injury

To minimize the risk of renal injury when using gentamicin, several factors should be considered:

• The dose and duration of gentamicin therapy should be carefully managed, as the nephrotoxic potential of aminoglycosides is primarily correlated to the duration of therapy 3.
• Extended interval dosing (EID) of gentamicin, which involves dosing every 24 hours, may be beneficial in reducing the risk of nephrotoxicity, but patients with impaired renal function may require a longer dose interval 4.
• Initial dose intervals for gentamicin of 24,36, and 48 hours are recommended for patients with creatinine clearance (CL(cr)) ≥ 60,40-59, and 20-39 mL/min, respectively 4.
• In critically ill patients, a once-daily dosage regimen of gentamicin is considered feasible, but the initial dose should be increased in septic patients due to the increased volume of distribution 5.
• Monitoring of renal function is crucial during gentamicin therapy, and specific microRNAs (miRNAs) may serve as biomarkers for early detection and monitoring of acute kidney injury (AKI) induced by gentamicin 6.

Risk Factors for Renal Injury

Certain patient populations are at higher risk for renal injury due to gentamicin, including:

• Elderly patients 7
• Patients with pre-existing renal impairment or kidney abnormalities 7, 4
• Patients receiving high-dose or prolonged gentamicin therapy 6
• Patients with sepsis or critical illness 5

Management of Gentamicin-Induced Renal Injury

If renal injury occurs due to gentamicin, management strategies may include:

• Discontinuation of gentamicin therapy 7
• Monitoring of renal function and adjustment of dose intervals or discontinuation of therapy as needed 4, 5
• Use of alternative antibiotics or therapies 3