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 an tibiotics administered in a prophylactic dose to children with vesicoureter al reflux. Materials and Methods: A total of 159 urine samples from 53 children taking prophylactic antibiotics with proved vesicoureteral reflux were tested. Th e children were divided into 4 groups according to the antibiotic given, wh ich 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, an d growth inhibition by this specific volume was equivalent to that produced by standard diffusion disks. In addition, the specific gravity, which refl ected 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 c otrimoxazole and 47 +/- 35 months for cefixime, respectively. In children l ess 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 high er in the afternoon and evening hours (1.019 +/- 0.003 versus 1.007 +/- 0.0 03 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 cefixim e, respectively (p <0.001 far cotrimoxazole and cefixime versus nalidixic a cid and cephalexin. Divided into morning, noon and evening, the percentage of samples that demonstrated growth inhibition was 85.7%, 21.4% and 7.1% fo r 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 inhibiti on (r = 0.55, p (0.001). Conclusions: Urine concentration during the day is dependent on age with ol der 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 bacteri cidal effect for about 60% of a 24-hour day due to the longer half-life.