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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.
Meropenem | Index | Doxycycline |
Index: 1–9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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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