Gentamicin is an aminoglycoside antibiotic that is usually used in combination to treat severe systemic infections that are due to sensitive Gram-negative and other organisms.
They include biliary tract infections, brucellosis, endometritis, gastroenteritis, cystic fibrosis as well as prophylaxis of surgical infections and the treatment of immunocompromised patients in intensive care.
Like other aminoglycosides, gentamicin synergizes with penicillins in killing Streptococcus faecalis in endocarditis.
Gentamicin sometimes can be used alone but usually in combination with other antibiotics such as penicillins or cephalosporins
Gentamicin is often used synergistically in combination with a-lactam antibiotics or vancomycin for serious infections that require broad coverage.
Aminoglycosides induce the binding of “wrong” t-RNA-AA complexes, resulting in the synthesis of false proteins. Aminoglycosides are bactericidal.
Aminoglycoside antibiotics consist of glycoside-linked amino-sugars. They contain numerous hydroxyl groups and amino groups that can bind protons. Hence, these compounds are highly polar, poorly membrane permeable, and not absorbed enterally.
Aminoglycosides gain access to the bacterial interior by the use of bacterial transport systems. In the kidney, they enter the cells of the proximal tubules via an uptake system for oligopeptide
Mechanism of Action:
- Binds irreversibly to the 30S ribosomal subunit
- Inhibits initiation complex formation
- Induces misreading of mRNA , producing abnormal or nonfunctional proteins
- Ultimately bactericidal
- Requires oxygen-dependent transport into bacteria, hence ineffective against anaerobes
Spectrum of Activity
- Primarily active against Gram-negative aerobes
- Limited Gram-positive activity; used synergistically with β-lactams for serious Gram-positive infections (e.g., Enterococcus faecalis in endocarditis)
Indications
Used alone or in combination therapy for severe systemic infections:
- Sepsis and bacteremia
- Endocarditis (with penicillin or vancomycin)
- Intra-abdominal infections (e.g., peritonitis)
- Complicated urinary tract infections (UTIs) (not for uncomplicated UTI)
- Bone and joint infections (e.g., osteomyelitis)
- Skin and soft tissue infections (e.g., infected burns, cellulitis)
- Pneumonia (typically nosocomial, in combination)
- Eye infections (topical drops)
Pharmacokinetics
- Route of Administration:
- Intramuscular (IM) or intravenous (IV)
- Topical for ocular infections
- Absorption: Poor oral absorption
- Distribution:
- Poor CSF penetration
- Low protein binding (~30%)
- Excretion:
- Renal (unchanged)
- Adjust dose in renal impairment
- Half-life: Prolonged in neonates and renal dysfunction
Dosing
- Standard dose: 3–5 mg/kg/day divided every 8 hours (q8h)
- Extended interval dosing (once daily) may reduce toxicity
Mechanism of Resistance
- Plasmid-mediated enzymatic inactivation
- Altered ribosomal binding site
- Decreased drug uptake or efflux
Side Effects (Dose & Duration Dependent)
1. Nephrotoxicity
- Accumulates in renal proximal tubules
- Often reversible
- Risk ↑ in elderly, dehydration, renal disease
2. Ototoxicity
- Damage to cochlear (hearing loss) and vestibular (balance) systems
- Irreversible
- Symptoms: tinnitus, vertigo, hearing loss
- Risk ↑ with prolonged use or high serum levels
3. Neuromuscular Blockade
- Rare, can cause respiratory paralysis
- Risk ↑ with anesthetics or neuromuscular blockers
- Antidotes: Calcium gluconate, Neostigmine
4. Others
- Hypomagnesemia (prolonged use)
- Antibiotic-associated colitis (e.g., C. difficile )
- Stomatitis, nausea, vomiting
- Rash and hypersensitivity reactions
Contraindications
- Known hypersensitivity to gentamicin or other aminoglycosides
- Myasthenia gravis (can worsen symptoms)
- Pregnancy (Category D: potential for fetal ototoxicity)
- Use cautiously in:
- Parkinsonism
- Premature neonates (immature renal function)
- Patients receiving loop diuretics (e.g., furosemide)
Drug Interactions
- ↑ Nephrotoxicity:
- Other aminoglycosides
- Vancomycin
- Amphotericin B
- Cisplatin, Cyclosporine
- ↑ Ototoxicity:
- Loop diuretics (e.g., furosemide, ethacrynic acid)
- ↑ Neuromuscular blockade:
- Non-depolarizing neuromuscular blockers
Monitoring Parameters
- Serum gentamicin levels:
- Trough (<2 µg/mL) before next dose
- Peak (4–10 µg/mL) after administration
- Monitor renal function (BUN, creatinine)
- Watch for signs of ototoxicity and neuromuscular weakness
Toxicity and Overdose
- Serum levels >12 µg/mL increase toxicity risk
- Treatment:
- Hemodialysis or peritoneal dialysis
- Stop drug immediately
- Monitor hearing and renal function
High-Yield Points
- Not effective against anaerobes
- Used synergistically with β-lactams or vancomycin
- Narrow therapeutic index – serum level monitoring critical
- Nephrotoxicity and ototoxicity are the most dangerous adverse effects
- Extended interval dosing may reduce toxicity
- Avoid in pregnancy unless life-saving
