Makindo Medical Notes.com

Gentamicin is toxic to cochlear hair cells, and it is known to disrupt mitochondrial protein synthesis, which leads to increased oxygen free radical generation via inducible nitric oxide synthase activity. Please note that the maximum dose in patients >65 years of age, regardless of renal function, is 3mg/kg.

About: Always check the BNF link here

• Aminoglycoside used for severe infections
• It is Ototoxic and nephrotoxic
• Toxicity increased by Loop diuretics
• Best given once a day 5-7 mg/kg/day
• Exception is Endocarditis at 1 mg/kg/8h
• Trough level (before next dose) <1mg/L

Mode of action

• Binds irreversibly to the bacterial ribosomal 30s subunit
• Causes misreading of mRNA codons. Bactericidal

Gentamicin provides excellent Gram-negative coverage, commonly used in the surgical setting for prophylaxis, and is still considered top-line therapy for patients with suspected Gram-negative sepsis.

Indications

• Severe infections, Infective endocarditis (with penicillin)
• Anti Staphylococcal, pyelonephritis, septicaemia
• Gram negative aerobic cover
• Septicaemia and neonatal sepsis (often with Penicillin/Metronidazole)
• Pyelonephritis, Biliary tract infections
• Aerobic gram-negative rods - Pseudomonas, Proteus, Anti- Staphylococcal
• Streptococci are resistant unless combined with penicillin

Ineffective

• Fungi, viruses, Anaerobic bacteria

Dose: Any total daily dose over 480 mg needs specialist advice

• Septicaemia, meningitis, biliary tract infection, pyelonephritis, endocarditis, pneumonia, prostatitis
• Gentamicin 3-5 mg/kg/day in 3 divided doses 8 h IV
• Once daily dosing: Gentamicin 5-7 mg/kg/day IV OD
• G+ve endocarditis or HACEK endocarditis (with other antibacterials): Gentamicin 1 mg/kg 12 h slow IV over 3 mins/IM.

More information on Dosing

• Before dosing need to know sex, age, height, weight and creatinine (if known).
• Use these to calculate the Gentamicin dose and frequency.

Dose range: You must check with BNF or drug datasheet

Notes

• *Standard indications are Septicaemia, Meningitis and other CNS infections, Biliary-tract infection, Endocarditis, Pneumonia in hospital patients, Adjunct in listerial meningitis, Prostatitis
• To avoid excessive dosage in obese patients, use ideal weight for height to calculate parenteral dose and monitor serum-Gentamicin concentration closely.
• Excretion of aminoglycosides is principally via the kidney and accumulation occurs in renal impairment. Ototoxicity and nephrotoxicity occur commonly in patients with renal failure.
• In adults A once-daily, high-dose regimen of an aminoglycoside should be avoided in patients with a creatinine clearance less than 20 mL/ minute.
• Serum concentration monitoring avoids both excessive and subtherapeutic concentrations thus preventing toxicity and ensuring efficacy.
• Measure Gentamicin levels in all patients receiving parenteral Gentamicin
• Measure Gentamicin levels must be determined in the elderly.
• In patients with normal renal function, aminoglycoside concentrations should be measured after 3 or 4 doses of a multiple daily dose regimen and after a dose change.

Multiple daily dose regimens

• Gentamicin levels should be taken approximately 1 hour after IM/IV injection (Peak)
• Gentamicin levels should be taken just before the next dose (Trough)
• If trough concentration is high, the interval between doses must be increased.
• If peak concentration is high, the dose must be decreased.
• Standard: Peak 5-10 mg/litre Trough < 2 mg/litre.
• Endocarditis: Peak 3-5 mg/litre Trough < 1 mg/litre.
• Cystic fibrosis: Peak 8-12 mg/litre Trough < 2 mg/litre.
• Serum-Gentamicin concentration should be determined twice each week and more in renal impairment

Once daily dose regimens

• As effective as multiple dosing regimes
• Less toxic (less nephrotoxicity & ototoxicity)
• More convenient to administer and monitor
• More economical

Prescribing

• Give the recommended dose by infusion in 100ml sodium chloride 0.9% over 30 minutes

First dose: Follow local guidance

Side effects

• Vestibular and ototoxicity due to Gentamicin is independent of drug concentration and is suggested by any of the following: dizziness, unsteadiness on feet, tinnitus, bobbing oscillopsia (vertical bouncing of surroundings), hearing loss, nausea or vomiting. Although toxicity is usually associated with prolonged aminoglycoside use it can also be idiosyncratic. All patients receiving Gentamicin therapy should be warned of these potential side effects and the drug should be discontinued at the earliest sign of toxicity.
• Patients may be asymptomatic but still have toxic Gentamicin levels and toxicity can develop even in patients with normal Gentamicin levels. The best way of avoiding toxicity is to ensure that treatment duration is no more than 3 days unless this is necessary on clinical grounds.

Monitoring

• Peak dose at 1 hour post dose 5-10 mg/l or 9-18 micromoles/L.
• Trough dose taken before dose given < 2 mg/l or 4.2 micromoles/L
• Toxic > 12 mg/L (22 micromol/L)
• Toxicity: Tinnitus, deafness, nystagmus, vertigo, AKI

Interactions

• Gentamicin ototoxicity increased Ciclosporin and cytotoxics
• Gentamicin nephrotoxicity increased by loop diuretics
• Discuss with pharmacy and consult BNF
• May block effects of Pyridostigmine and neostigmine

Cautions

Contraindications

• Myasthenia Gravis, Hypersensitivity to aminoglycosides
• Multiple myeloma, Severe renal impairment
• Pregnancy - Can cross the placenta to cause fetal VIII nerve damage

Side effects

• Ototoxic (Vestibular part of VIIIth) Balance more than auditory
• Nephrotoxic, Hypersensitivity, Rash, Nausea and vomiting, seizures
• Neuromuscular blockade - Can worsen myasthenia gravis

Renal

• Excretion of aminoglycosides is principally via the kidney and accumulation occurs in renal impairment. Ototoxicity and nephrotoxicity occur commonly in patients with renal failure.
• A once-daily, high-dose regimen of an aminoglycoside should be avoided in patients with a creatinine clearance of less than 20 mL/ minute.
• If there is impairment of renal function, the interval between doses must be increased; if the renal impairment is severe, the dose itself should be reduced as well.
• Serum-aminoglycoside concentrations must be monitored in patients with renal impairment; earlier and more frequent measurement of aminoglycoside concentration may be required.

References

• Summary Product Characteristics