Is It Ever Safe to Administer Aminoglycosides?

ISSUE

Aminoglycosides have excellent gram-negative spectrum but poor activity against anaerobes and in abscesses.¹ The main limitations of aminoglycoside use are dose-dependent nephrotoxicity and ototoxicity, which are caused by the local generation of superoxide and other free radicals.²

ANSWERS

Aminoglycosides are still indicated for human patients with acute pyelonephritis, intraabdominal infections, osteomyelitis, and pneumonias associated with cystic fibrosis.³

In dogs and cats, aminoglycosides are often the most cost-effective and convenient option for resistant isolates of Escherichia coli, Pseudomonas spp,⁴ and methicillin-resistant Staphylococcus spp.⁵ Despite the intrinsic toxicity of aminoglycosides, several key management points can optimize their safe and effective use.

GENERAL

Use once-a-day dosing

Aminoglycosides should be given once a day, which is more convenient than and (at least) as effective as administering 3 times a day.

• Once-a-day dosing may also be associated with less risk for nephrotoxicity.⁶

  • Lower trough urinary concentrations may result in less overall uptake into renal tubular cells.

• Gentamicin sulfate: 6-8 mg/kg IV, IM, or SC (less painful) once a day

• Amikacin: 10-15 mg/kg IV, IM, or SC (less painful) once a day

  • May show lower minimum inhibitory concentrations (MICs) than gentamicin does against some gram-negative and mycobacterial isolates^7,8

Monitor patient status

• Make sure the patient is hydrated.⁹

  • Consider concurrent IV or SC fluids.

• Monitor urine sediment.

  • Monitor for tubular damage via daily examination of fresh urine sediment for granular casts.⁹

Minimize treatment duration

• Limit aminoglycoside therapy to 5 or fewer days¹⁰ when possible.

Avoid toxic drug interactions

Furosemide

• Systemic aminoglycosides should be avoided in patients being treated with furosemide, as the combination can increase nephrotoxicity and ototoxicity.¹¹

Cisplatin

• Aminoglycosides should be avoided in cancer patients being treated with cisplatin.¹²

  • Cisplatin also can lead to dose-dependent nephrotoxicity and ototoxicity.

Consider other potential measures to prevent toxicity

• Silymarin (20 mg/kg PO once a day) and vitamin E (25 mg/kg PO once a day) can decrease aminoglycoside nephrotoxicity in dogs experimentally.¹³

  • Needs to be assessed in clinical patients

• Melatonin, which has antioxidant properties, has been shown to decrease aminoglycoside nephrotoxicity in rodents.^14,15

  • Has not been evaluated in dogs or cats

SPECIFICS

Use extra caution in patients with renal failure

• In patients with renal insufficiency, choose other agents when possible.

  • Ask for susceptibilities to additional agents (eg, ticarcillin, cefotetan, aztreonam, meropenem).

• When aminoglycosides are necessary for patients with preexisting renal failure, extend the dosing interval¹⁶ (eg, to every other day).

  • To minimize toxicity, aim for a serum trough level <2 μg/mL.¹⁷

• Always rehydrate the patient and use concurrent fluid therapy (IV or SC).