Effect of urine osmolality on the antibacterial activity of gentamicin

Gentamicin is often used for the treatment of urinary tract infection. The dosage recommendations for gentamicin in this condition have not been properly determined, nor has the issue of whether one should maintain an increased urine flow been resolved. Urinary concentrations of gentamicin were measured in mongrel dogs 0-4 hours (early samples) and 24-28 hours (late samples) after a single 2 mg/kg i.m. dose by R.I.A. The MBC of gentamicin against an E. coli strain was determined in broth medium and in dog urine. Urinary concentrations of gentamicin ranged from 6.2 to 1161 micrograms/ml in early samples and from 0.2 to 12.5 mu/ml in late samples, depending on urine osmolality. MBC of gentamicin in heart-brain broth was 1.5-3.0 micrograms/ml whereas in urine it ranged from 0.045-0.09 to 50-100 micrograms/ml; MBC of gentamicin in dilute urine was lower than in concentrated urine (r = 0.85, P less than 0.01). However "late" dilute and concentrated urine samples allowed bacterial growth. Use of gentamicin in urinary tract infection could therefore require smaller than the recommended doses for systemic infections. Also, it seems reasonable to advise the avoidance of urine of extreme osmolalities. A study in patients should verify the clinical relevance of the findings of this study.