A bioassay evaluation of the urinary antibacterial efficacy of low dose prophylactic antibiotics in children with vesicoureteral reflux

Purpose: We evaluated by means of a bioassay the efficacy of 4 different antibiotics administered in a prophylactic dose to children with vesicoureteral reflux. Materials and Methods: A total of 159 urine samples from 53 children taking prophylactic antibiotics with proved vesicoureteral reflux were tested. The children were divided into 4 groups according to the antibiotic given, which included nalidixic acid, cephalexin, cotrimoxazole and cefixime. Urine samples were collected in the morning, at noon and in the evening, and each sample was bioassayed for growth inhibition of a standard Escherichia coli. The urine volume used was specifically determined for each antibiotic, and growth inhibition by this specific volume was equivalent to that produced by standard diffusion disks. In addition, the specific gravity, which reflected urinary concentration of each sample, was measured. Results: Mean patient age plus or minus standard deviation of the 4 groups was 53 +/- 41 for nalidixic acid, 23 +/- 34 for cephalexin, 55 +/- 35 for cotrimoxazole and 47 +/- 35 months for cefixime, respectively. In children less than 2 years old specific gravity was higher in the morning(1.021 +/- 0.0006 versus 1.0008 +/- 0.0004 at 8 a.m. and 2 p.m., respectively, p <0.05). In contrast, in children alder than 4 years the specific gravity was higher in the afternoon and evening hours (1.019 +/- 0.003 versus 1.007 +/- 0.003 at 2 p.m. and 8 a.m., respectively, p <0.05). The percentage of patients who demonstrated growth inhibition in all 3 samples of the test day was 7%, 6%, 69% and 44% for nalidixic acid, cephalexin, cotrimoxazole and cefixime, respectively (p <0.001 far cotrimoxazole and cefixime versus nalidixic acid and cephalexin. Divided into morning, noon and evening, the percentage of samples that demonstrated growth inhibition was 85.7%, 21.4% and 7.1% for nalidixic acid, 37.5%, 12.5% and 6.3% far cephalexin, 100%, 92.3% and 76.9% for cotrimoxazole and 100%, 77.7% and 55.5% for cefixime, respectively. A direct correlation was found between specific gravity and growth inhibition (r = 0.55, p (0.001). Conclusions: Urine concentration during the day is dependent on age with older children having more concentrated urine in the latter part of the day. Growth inhibition is enhanced by concentrated urine. Compared to nalidixic acid and cephalexin, cotrimoxazole and cefixime produce a sustained bactericidal effect for about 60% of a 24-hour day due to the longer half-life.