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Gentamicin: Mechanism of Action, Side Effects and Dosage

Gentamicin is an aminoglycoside antibiotic primarily effective against gram-negative bacteria. Due to its side effects, it is only used to treat life-threatening infections or multi-resistant pathogens.

Mechanism of Action:

Gentamicin has a bactericidal effect: it inhibits bacterial protein biosynthesis by binding to the 30S subunit of the ribosome, which leads to defective proteins and damage to the cell wall.

Antibiotic Spectrum of Gentamicin:

Active against gram-negative bacteria: E. coli, Klebsiella, Proteus, Enterobacter, Haemophilus, Pseudomonas, Citrobacter, and Serratia. Gentamicin exhibits only weak efficacy against gram-positive bacteria (enterococci, streptococci, and staphylococci), as its penetration through the thick bacterial wall is difficult. However, there is a synergistic effect when combined with antibiotics that act on the bacterial cell wall, making combinations of gentamicin and a β-lactam-antibiotic very effective.

Urological Indications for Gentamicin:

Gentamicin, in combination with acylaminopenicillins or third-generation cephalosporins, is a good alternative to carbapenems for the treatment of life-threatening or therapy-resistant, complicated urinary tract infections (pyelonephritis, catheter-associated infections, prostatitis, epididymitis) and urosepsis. Furthermore, a single dose of gentamicin in combination with a β-lactam antibiotic is an option for perioperative prophylaxis in risk patients for a gram-negative infection (e.g., TURP in patients with indwelling catheters). Gentamicin is only used as monotherapy for urinary tract infections if the antibiogram offers no other alternatives.

Pharmacokinetics of Gentamicin:

• Only parenteral administration is possible (slowly i.v. over 30–60 min or i.m.).
• Good distribution in the extracellular space but poor penetration into the bone and CNS.
• Unchanged renal elimination, half-life 2–3 hours with normal kidney function.

Side Effects of Gentamicin

Due to its potentially significant side effects, gentamicin is only used in cases of life-threatening infections or multi-resistant pathogens. A single daily dose of gentamicin is less toxic than multiple-dosing regimens.

• Kidneys: reversible nephrotoxicity, characterized by proteinuria and elevated creatinine levels. 
• CNS: potentially irreversible ototoxicity, neurotoxicity, and neuromuscular blockade with risk of respiratory paralysis in myasthenia gravis.
• Other: allergic reactions and fever.

Drug Interactions:

Be cautious when administering gentamicin with other nephrotoxic or ototoxic drugs, such as amphotericin B, cyclosporine, cisplatin, loop diuretics, or vancomycin.

Contraindications:

Allergy to gentamicin or other aminoglycosides, severe renal insufficiency, pre-existing hearing loss, pregnancy, myasthenia gravis.

Dosage of Gentamicin

• 3 mg/kgBW once daily i.v. for patients with normal kidney function; the maximum dose for severe infections and resistant pathogens is 6 mg/kgBW.
• For patients with renal insufficiency, it is essential to reduce the dose of subsequent administrations after the first normal dose to avoid toxic side effects:
  • 80% of the daily dose for a GFR of 100–71 ml/min,
  • 65% of the daily dose for a GFR of 70–56 ml/min,
  • 55% of the daily dose for a GFR of 55–46 ml/min,
  • 45% of the daily dose for a GFR of 45–36 ml/min,
  • 30% of the daily dose for a GFR of 35–26 ml/min,
  • 20% of the daily dose for a GFR of 25–16 ml/min,
  • and only 10% of the daily dose below that.
• Monitoring the trough level of gentamicin concentration (blood sample taken towards the end of the dosing interval) serves to rule out accumulation; this should not exceed 1 mg/l with once-daily dosing. Therapeutic drug monitoring is critical in patients with impaired renal function, high dosages, or treatment over seven days.

References

Santucci und Krieger 2000 SANTUCCI, R. A. ; KRIEGER, J. N.: Gentamicin for the practicing urologist: review of efficacy, single daily dosing and switch therapy.
In: J Urol
163 (2000), Apr, Nr. 4, S. 1076–1084

Simon und Stille 1997 SIMON, C. ; STILLE, W.: Antibiotika-Therapie in Klinik und Praxis.
9. Auflage.
Stuttgart New York : Schattauer, 1997

  Deutsche Version: Pharmakologie und Nebenwirkungen von Gentamicin

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This website is designed for physicians and medical professionals. It presents diseases of the genital organs through detailed text and images. Some content may not be suitable for children or sensitive readers. Many illustrations are available exclusively to Steady members. Are you a physician and interested in supporting this project? Join Steady to unlock full access to all images and enjoy an ad-free experience. Try it free for 7 days—no obligation.