Gentamicin
Gentamicin
Generic Name
Gentamicin
Mechanism
- Inhibits Protein Synthesis by binding to the 30S ribosomal subunit, causing misreading of mRNA and premature chain termination.
- Produces a *bactericidal* effect that is both time‑dependent (microbial kill increases with drug concentration > MIC) and concentration‑dependent (higher peaks → more bacterial clearance).
> Key Point: Gentamicin’s unique property is a *post‑inhibitory effect*—bacteria continue to be killed for a period after drug levels fall below the MIC.
---
Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Poor oral (≤10%) | Usually IV or IM |
| Distribution | 0.3 L/kg; limited penetration into CSF, pleural fluid | High protein binding (~35–40%) |
| Elimination | Renal (≈90%) | Clearance ≈ 0.1 L/h/kg; half‑life ≈ 2–3 h (creatinine clearance 10–120 mL/min) |
| Volume of Distribution | 0.25–0.3 L/kg | Smaller in elderly/dermal loss patients |
| Metabolism | None | No hepatic metabolism, so minimal drug‑drug interactions |
> Toxicity Link: Nephro‑ and ototoxicity correlate with *area‑under‑curve (AUC)* and *peak concentrations*.
--
•
Indications
- Life‑threatening infections caused by gram‑negative organisms:
- *Pseudomonas aeruginosa* (lung, bloodstream, wound)
- *Escherichia coli*, *Klebsiella*, *Proteus*, *Enterobacter* species
- Septicemia, peritonitis, osteomyelitis, meningitis (with proper CSF penetration).
- Combination therapy with β‑lactams or carbapenems for severe polymicrobial infections.
- Treatment of *Acinetobacter* species when susceptible.
---
Contraindications
- Absolute Contraindications
- Known hypersensitivity to gentamicin or other aminoglycosides.
- Pregnant women (category C) – avoid near term.
- Warnings
- *Nephrotoxicity*: dose‑dependent tubulointerstitial damage.
- *Ototoxicity*: cochlear and vestibular dysfunction, dose‑dependent.
- *Neuromuscular blockade*: potentiates neuromuscular blocking agents.
- *Cardiovascular*: may cause arrhythmias in susceptible patients.
- Precaution
- Renal impairment: use renal‑dose adjustments.
---
Dosing
| Population | Loading Dose | Maintenance Dose | Administration |
| Adults (≥70 kg, normal renal) | 7.5 mg/kg IV (single dose) | 7.5 mg/kg IV q24 h (or q48 h) | IV or IM, preferably once daily for peak‑to‑trough optimization |
| Renal impairment (CrCl 30–60 mL/min) | 7.5 mg/kg IV | 5 mg/kg IV q24 h | Use renal‑dose adjustment formulas |
| Children (2–12 yr) | 4 mg/kg IV | 4 mg/kg IV q24 h | Adjust per weight & renal function |
| <2 yr / <20 kg | 4 mg/kg IV | 4 mg/kg IV q24 h | Titrate cautiously; monitor AUC |
• Peak Levels: 5–10 µg/mL (for serious infections).
• Trough Levels: <2 µg/mL (ideally <0.5 µg/mL for high‑risk patients).
• TDM (therapeutic drug monitoring) is mandatory to adjust dose and schedule.
--
•
Adverse Effects
- Common
- Nephrotoxicity (azotemia, proteinuria).
- Ototoxicity (tinnitus, hearing loss).
- Hypotension (rare, but possible).
- Rash or mild hypersensitivity reactions.
- Serious
- Sensorineural hearing loss (irreversible, often dose‑related).
- Vestibular symptoms: vertigo, imbalance.
- Renal failure (acute tubular necrosis).
- Neuromuscular blockade: respiratory depressant effect.
- Rash → anaphylaxis (rare).
---
Monitoring
| Parameter | Frequency | Target |
| Serum gentamicin peak & trough | Before 2nd dose (IV) | 5–10 µg/mL peak; 20 dB |
| Vestibular function | Baseline; then bi‑weekly | No new vertigo or imbalance |
| Electrolytes | Every 2–3 days | Monitor for hypokalemia, hypomagnesemia |
--
•
Clinical Pearls
- Single‑Daily Dosing Is Key: Once‑daily (q24 h) dosing maximizes peak levels while allowing troughs to fall below 2 µg/mL, reducing toxicity without compromising efficacy.
- Use TDM Early: Aim to draw trough levels 30 min before the next dose on day 3–5 to avoid accumulation in renal impairment.
- Renal Index Formula:
- *Dose (mg) = 7.5 mg/kg × (CrCl/120) (for CrCl 30–120 mL/min).*
- Never forget to convert to renal dose if CrCl <30 mL/min—use a loading dose of 5 mg/kg followed by lower maintenance doses or intermittent dosing (q48 h).
- Ototoxicity Prevention: Combine gentamicin with a non‑aminoglycoside (e.g., β‑lactam) and avoid concurrent loop diuretics or other ototoxic agents.
- Nephrotoxicity Monitoring: Track serum creatinine after each dose until plateau; a ≥30% rise warrants dose readjustment or discontinuation.
- Pregnancy Note: Animal studies show fetal harm; use only if benefits outweigh risks and alternative agents are unsuitable.
- Use in Sepsis: Pair with a β‑lactam or carbapenem; avoid monotherapy in MDR gram‑negative infections unless susceptibility confirmed.
--
• References
• Tripathi K. *Goodman & Gilman’s The Pharmacological Basis of Therapeutics.* 13th ed.
• WHO Drug Information, 2024.
• American Society for Clinical Pharmacology & Therapeutics (ASCPT) guidance on aminoglycoside monitoring.