Amikacin

# Amikacin ## Overview - **Classification**: Aminoglycoside antibiotic - **Mechanism**: Irreversibly binds to the bacterial 30S ribosomal subunit, inhibiting protein synthesis. This leads to bactericidal action. ## Primary Indications 1. **Serious Gram-Negative Infections**: Especially multi-drug resistant strains of *Pseudomonas aeruginosa*, *Klebsiella*, *Enterobacter*, *Serratia*. Often used in combination with beta-lactams. 2. **Mycobacterial Infections**: Part of multi-drug regimens for drug-resistant tuberculosis (MDR-TB) and atypical mycobacterial infections. 3. **Febrile Neutropenia**: Empiric therapy in combination with other broad-spectrum antibiotics. ## Adult Dosing ### Standard Dosing **Serious Gram-Negative Infections (Once-Daily Dosing)** - **Dose**: **15-20 mg/kg** (ideal or adjusted body weight) - **Frequency**: Every **24 hours (q24h)** - **Route**: Intravenous (IV) infusion over 30-60 minutes - **Duration**: Typically **7-10 days**, adjust based on infection severity and source control. **Serious Gram-Negative Infections (Conventional Dosing)** - **Dose**: **5-7.5 mg/kg** (ideal or adjusted body weight) - **Frequency**: Every **8 hours (q8h)** - **Route**: Intravenous (IV) or Intramuscular (IM) - **Special Considerations**: Once-daily dosing is generally preferred due to better safety profile. **Mycobacterial Infections (e.g., MDR-TB)** - **Dose**: **15 mg/kg** - **Frequency**: **3-5 times per week** (depending on specific regimen) - **Route**: Intravenous (IV) or Intramuscular (IM) - **Maximum**: **1.0-1.5 grams/day** ### Dose Adjustments - **Renal Impairment**: Requires significant dose reduction or interval extension. Therapeutic drug monitoring (TDM) is essential. - **CrCl >60 mL/min**: No adjustment. - **CrCl 30-60 mL/min**: Extend interval (e.g., q12-24h for conventional) or reduce dose for once-daily. - **CrCl 10-29 mL/min**: Further extend interval (e.g., q24-48h for conventional). - **CrCl <10 mL/min or HD**: Administer **25-50%** of normal dose after dialysis. - **Hepatic Impairment**: No specific dose adjustment needed. - **Elderly Patients**: Monitor renal function closely as age-related decline is common. Consider lower end of dosing range. ## Pediatric Dosing ### Neonates (0-28 days) - **Dose**: **7.5 mg/kg** - **Frequency**: Every **12-24 hours (q12-24h)** based on gestational and postnatal age. - **Maximum**: **15 mg/kg/day** - **Special Notes**: Extended interval dosing often preferred. Close TDM is crucial due to variable renal maturation. ### Infants (1-12 months) - **Dose**: **15-20 mg/kg** (for once-daily) or **5-7.5 mg/kg** (for q8h) - **Frequency**: Every **24 hours (q24h)** (once-daily) or Every **8 hours (q8h)** (conventional) - **Maximum**: **1.5 grams/day** ### Children (1-12 years) - **Dose**: **15-20 mg/kg** (for once-daily) or **5-7.5 mg/kg** (for q8h) - **Frequency**: Every **24 hours (q24h)** (once-daily) or Every **8 hours (q8h)** (conventional) - **Maximum**: **1.5 grams/day** ### Adolescents (13-18 years) - **Dose**: Follow **adult dosing** guidelines. - **Maximum**: **1.5 grams/day** ## Safety Information ### Contraindications - **Absolute**: History of serious hypersensitivity to amikacin or other aminoglycosides. - **Absolute**: Myasthenia gravis (can exacerbate muscle weakness). - **Relative**: Pre-existing hearing loss or vestibular dysfunction. ### Common Adverse Effects - **Common (1-10%)**: Nephrotoxicity (elevated creatinine, decreased urine output), Ototoxicity (tinnitus, hearing loss, vertigo, dizziness). - **Serious but Rare**: Neuromuscular blockade (respiratory depression), Anaphylaxis, Stevens-Johnson syndrome. ### Key Drug Interactions - **Loop Diuretics (e.g., Furosemide)**: Increased risk of ototoxicity. Monitor audiometry if concurrent use necessary. - **Other Nephrotoxic Drugs (e.g., Vancomycin, NSAIDs, Amphotericin B)**: Increased risk of nephrotoxicity. Monitor renal function frequently. - **Neuromuscular Blockers**: Potentiates muscle relaxation, potentially causing respiratory depression. Use with extreme caution. - **Penicillins/Cephalosporins**: Physical incompatibility *in vitro*; administer separately. ## Monitoring & Follow-up - **Before Treatment**: Baseline renal function (SCr, BUN, CrCl), Audiogram (if baseline hearing concerns). - **During Treatment**: - **Renal Function**: SCr and BUN **daily or every 2-3 days**. - **Drug Levels**: **Peak and trough levels** (for conventional dosing) or **random level 6-12h post-dose** (for once-daily dosing) as per local protocol. - **Urine Output**: Monitor for changes. - **Audiologic monitoring**: Especially for prolonged therapy or high-risk patients. - **Clinical Signs**: Watch for signs of ototoxicity (tinnitus, vertigo, hearing changes), and nephrotoxicity (oliguria, edema). ## Clinical Pearls - 💡 **Therapeutic Drug Monitoring (TDM)** is critical to balance efficacy and minimize toxicity, especially in renal impairment. - 💡 **Once-daily dosing** is preferred for most indications due to reduced nephrotoxicity and ototoxicity compared to conventional dosing. - 💡 Ensure **adequate hydration** to help reduce the risk of nephrotoxicity. - 💡 Amikacin is **not effective against anaerobes** and has limited activity against Gram-positive bacteria. - 💡 **Counsel patients** to report any ringing in ears, dizziness, or changes in hearing immediately. > **⚠️ Important**: This information is for educational purposes only. Always consult current prescribing information, local guidelines, and clinical judgment before prescribing.