Gentamicin

Gentamicin, Streptomycin, Neomycin, Tobramycin, Amikacin - Aminoglycosides

Mechanism of Action

Pharmacology - Vancomycin vs. Gentamicin Antibiotics

Gentamicin is a potent antibiotic that belongs to the aminoglycoside class of medications. It is widely used in the medical field to treat a variety of bacterial infections, particularly those caused by Gram-negative bacteria. This note provides an overview of gentamicin, including its mechanism of action, uses, administration, side effects, and considerations for use.

Mechanism of Action

Gentamicin works by binding to the 30S subunit of the bacterial ribosome, which is a critical component of the protein synthesis machinery in bacteria. By interfering with the ribosome's function, gentamicin inhibits the synthesis of proteins necessary for bacterial growth and survival. This action ultimately leads to the death of the bacterial cells, making gentamicin a bactericidal antibiotic.

Clinical Uses

Gentamicin is primarily used to treat serious infections caused by Gram-negative bacteria, including:

• Urinary Tract Infections (UTIs): Often used when the infection is caused by bacteria such as Escherichia coli or Klebsiella species.
• Respiratory Tract Infections: Effective against pneumonia and other respiratory infections caused by susceptible bacteria.
• Sepsis: Used in the treatment of bloodstream infections, particularly those caused by Gram-negative organisms.
• Intra-abdominal Infections: Often used in combination with other antibiotics to treat complex infections within the abdominal cavity.
• Skin and Soft Tissue Infections: Employed in cases where the infection is severe and caused by susceptible bacteria.

Administration

Gentamicin is typically administered via intravenous (IV) or intramuscular (IM) injection. The dosage and duration of treatment depend on the type and severity of the infection, as well as the patient's kidney function. It is crucial to monitor blood levels of gentamicin to avoid toxicity, as the drug has a narrow therapeutic index.

Side Effects

While gentamicin is effective in treating serious infections, it is associated with several potential side effects, including:

• Nephrotoxicity: Gentamicin can cause damage to the kidneys, leading to impaired kidney function. Monitoring kidney function during treatment is essential.
• Ototoxicity: The drug can also affect the auditory and vestibular systems, potentially leading to hearing loss or balance issues. This side effect is often irreversible.
• Neuromuscular Blockade: In rare cases, gentamicin can interfere with neuromuscular transmission, leading to muscle weakness or paralysis.
• Allergic Reactions: Some patients may experience allergic reactions, ranging from mild skin rashes to severe anaphylaxis.

Considerations for Use

When prescribing gentamicin, healthcare providers must consider several factors to ensure safe and effective use:

1. Renal Function: Due to the risk of nephrotoxicity, it is crucial to assess the patient's kidney function before and during treatment. Dosage adjustments may be necessary for patients with impaired renal function.
2. Therapeutic Drug Monitoring: Regular monitoring of gentamicin blood levels helps to maintain therapeutic efficacy while minimizing the risk of toxicity.
3. Combination Therapy: Gentamicin is often used in combination with other antibiotics to enhance its effectiveness and broaden the spectrum of antibacterial activity.
4. Patient History: A thorough patient history, including any previous adverse reactions to aminoglycosides, is essential to avoid potential complications.

ADVERSE EFFECTS

Adverse effects of gentamicin can range from less severe reactions such as nausea and vomiting to more severe reactions such as:

• Low blood counts
• Allergic responses
• Neuromuscular problems
• Nerve damage
• Kidney damage (nephrotoxicity)
• Ear disorders (ototoxicity)

Nephrotoxicity and ototoxicity are thought to be dose related with higher doses causing greater chance of toxicity.^[9] These two toxicities may have delayed presentation, sometimes not appearing until after completing treatment.^[9]

Kidney damage

Kidney damage is a problem in 10-25% of people who receive aminoglycosides, and gentamicin is one of the most nephrotoxic of the class.Oftentimes acute nephrotoxicity is reversible, but it may be fatal. The risk of nephrotoxicity can be affected by the dose, frequency, duration of therapy, and concurrent use of certain medications such as NSAIDs, diuretics, cisplatin, ciclosporin, cephalosporin, amphotericin, iodide contrast media, and vancomycin.

Factors that increase risk of nephrotoxicity include:

• Increased age
• Reduced renal function
• Pregnancy
• Hypothyroidism
• Hepatic dysfunction
• Volume depletion
• Metabolic acidosis
• Sodium depletion

Kidney dysfunction is monitored by measuring creatinine in the blood, electrolyte levels, low urine output, foamy urine, and concentrations of other chemicals in the blood.^[13]

Inner ear

11% of the population who receives aminoglycosides experience damage to their inner ear. The common symptoms of inner ear damage are: tinnitus, hearing loss, vertigo, trouble with coordination, dizziness. Chronic use of gentamicin can affect two area of the ears. First, damage of the inner ear hair cells can result in irreversible hearing loss. Second, damage to inner ear vestibular apparatus can lead to balance problems. To reduce the risk of ototoxicity it is recommended to stay hydrated.

Factors that increase risk of inner ear damage include:

• High blood uric acid levels
• Kidney dysfunction
• Liver dysfunction
• Higher doses
• Long courses of therapy
• Elderly
• Also taking strong diuretics (e.g. furosemide)

Contraindications

Gentamicin should not be used if a person has a history of hypersensitivity such as anaphylaxis shock or other serious toxic reaction to gentamicin or any other aminoglycosides.

ARTICLES/STUDIES

Propolis antibacterial and antioxidant synergisms with gentamicin and honey.

Protective Agents

• Methylcobalamin** is antagonist to the transient ototoxic action of gentamicin.
• Protective effects of **Zhibai Dihuang Wan** on renal tubular cells affected with gentamicin-induced apoptosis
• Crocus sativus** stigmas, tepals, and leaves ameliorate gentamicin-induced renal toxicity.
• Ameliorative effect of **gossypin** against gentamicin-induced nephrotoxicity in rats.
• Investigation of the effects of **crocin** on inflammation, oxidative stress, apoptosis, NF-κB, TLR-4 and Nrf-2/HO-1 pathways in gentamicin-induced nephrotoxicity in rats.
• Protective effect of **honey and propolis** against gentamicin-induced oxidative stress and hepatorenal damages.
• Protective and curative effects of ethanol extract of **Tinospora Cordifolia** on gentamicin-induced nephrotoxicity.
• Olive leaf extract** ameliorates gentamicin nephrotoxicity via antioxidant activity, increase of renal glutathione content, and increase of renal antioxidant enzymes activity, except for glutathione peroxidase.
• Glutamine** alleviates the renal dysfunction associated with gentamicin-induced acute kidney injury.
• Topical administration of **oleandrin** could protect against gentamicin ototoxicity via inhibition of activator protein-1 and c-Jun N-terminal kinase.
• *Punica granatum*** improves renal function in gentamicin-induced nephropathy in rats via attenuation of oxidative stress
• Evaluation of nephroprotective activity of **Musa paradisiac**a L. in gentamicin-induced nephrotoxicity.
• Lycopene** has a protective effect on gentamicin-induced oxidative stress and nephrotoxicity in rats.
• EGCG** protected outer hair cells from gentamicin toxicity in a cochlear explant model.
• Modulation of gentamicin-induced acute kidney injury by **myo-inositol oxygenase**.
• Watercress** can be suggested for prevention of Gentamicin induced nephrotoxicity.
• Bilberry** showed strong nephroprotective effect against gentamicin toxicity in rats.
• Rosemary and thyme** have potential renoprotective effects of against gentamicin toxicity in rats.
• Rosemary and thyme** extracts could be helpful in ameliorating some aspects of gentamicin toxicity.
• Nigella sativa** acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of gentamicin.
• N. sativa** may be useful in ameliorating signs of gentamicin nephrotoxicity in rats.
• Artichoke leaves extract** has nephroprotective potential against gentamicin in rats.
• The ototoxic effect generated by gentamicin could be ameliorated with the concurrent use of **naringenin**.
• Punica granatum** improves renal function in gentamicin-induced nephropathy.
• Protective effect of **selenium** on gentamicin-induced oxidative stress and nephrotoxicity.
• Melatonin** attenuates gentamicin-induced nephrotoxicity and oxidative stress.
• Vitamin D** attenuates gentamicin-induced acute renal damage via prevention of oxidative stress and DNA damage.
• Curcumin and vitamin C** attenuate gentamicin-induced nephrotoxicity.
• Potential effects of resatorvid and alpha lipoic acid on gentamicin-induced nephrotoxicity.