What is the recommended dose and mode of administration of gentamicin (an aminoglycoside antibiotic) for the treatment of brucellosis?

Gentamicin Dosage and Administration for Brucellosis Treatment

For brucellosis treatment, gentamicin should be administered at 5 mg/kg daily parenterally as a single dose for 7 days, in combination with doxycycline 100 mg twice daily orally for 6 weeks. 1, 2

Recommended Regimen Details

The doxycycline-gentamicin (DOX-GENT) combination is considered an adequate regimen for treating brucellosis with several key advantages:

• Dosage:

  • Gentamicin: 5 mg/kg daily parenterally as a single dose for 7 days
  • Doxycycline: 100 mg twice daily orally for 6 weeks (45 days)

• Evidence Level: BI (moderate to strong recommendation) 1, 2

• Administration Route:

  • Gentamicin: Intravenous (IV) or intramuscular (IM)
  • For IV administration: Dilute a single dose in 50-200 mL of sterile isotonic saline or 5% dextrose solution and infuse over 30 minutes to 2 hours 3

Advantages of DOX-GENT Regimen

• Wider availability of gentamicin compared to streptomycin
• Preserves streptomycin for tuberculosis treatment
• Comparable efficacy to the WHO-recommended doxycycline-streptomycin regimen
• Failure/relapse rates approximately 10-20% (about 5% higher than WHO-recommended regimens) 1
• Good safety profile with 7-day gentamicin course 4

Monitoring Recommendations

1. Serum Gentamicin Levels:

   • Peak concentration (30-60 minutes after administration): Target 4-6 mcg/mL
   • Avoid prolonged levels above 12 mcg/mL
   • Trough levels (just before next dose): Should be below 2 mcg/mL 3

2. Renal Function:

   • Monitor serum creatinine before and during treatment
   • Adjust dosage in patients with impaired renal function 3, 4

3. Follow-up:

   • Monitor for at least 2 years after treatment to detect recurrence 2

Dosage Adjustment for Renal Impairment

For patients with impaired renal function, dosage adjustment is essential:

1. Method 1: Increase interval between doses

   • Interval (hours) ≈ Serum creatinine (mg/100 mL) × 8

2. Method 2: Reduce dose but maintain 8-hour interval

   • Adjusted dose = Normal dose ÷ Serum creatinine level

3. Monitoring: Serum gentamicin levels should be measured to ensure adequate but not excessive levels 3

Alternative Regimens

If gentamicin is unavailable or contraindicated, consider these alternatives:

1. DOX-STR: Doxycycline 100 mg twice daily for 6 weeks + Streptomycin 15 mg/kg daily IM for 2-3 weeks (Evidence level: AI) 1, 2

2. DOX-RIF: Doxycycline 100 mg twice daily + Rifampicin 600-900 mg daily for 6 weeks (Evidence level: AI, but higher relapse rate) 1, 2

Special Populations

• Children <8 years: Avoid doxycycline; use rifampicin with cotrimoxazole for 45 days or rifampicin for 45 days with gentamicin 5-6 mg/kg/day for the first 5 days 5

• Pregnant women: Avoid doxycycline; rifampicin 900 mg once daily for 6 weeks is preferred 5

Clinical Pearls and Pitfalls

• Duration matters: Research shows that 45 days of doxycycline with 7 days of gentamicin has lower relapse rates (5.9%) compared to 30 days of doxycycline with 7 days of gentamicin (22.9%) 6

• Triple therapy consideration: Adding gentamicin for 7-10 days to doxycycline-rifampin can significantly decrease relapse rates compared to doxycycline-rifampin alone (4.6% vs 13.8%) 7

• Nephrotoxicity risk: Recent research confirms gentamicin is safe at 5 mg/kg/day for one week in brucellosis patients with normal renal function 4

• Dosing in obesity: Calculate gentamicin dosage based on lean body mass rather than actual body weight 3