Chromosome Studies of Pediatric Patients on Long-Term Nitrofurantoin or Furagin Therapy for Urinary Tract Infection. G. Slapsyte and J. Mierauskiene, Ecological Genetics Laboratory, Vilnius University, Ciurlionio 21, 2009 Vilnius, Lithuania
Nitrofurantoin and furagin are chemically and structurally similar 2-substituted 5-nitrofurans. Both of them possess excellent antibacterial activities and are widely used in the treatment of urinary tract infection (UTI). Earlier findings have indicated certain carcinogenic and genotoxic effects of nitrofurantoin. Little information exists on genetic effects of furagin. As both drugs are rather frequently used for a long-term low-dose antibacterial prophylaxis not only in adult patients but also in children, they have a certain priority for being tested for their genotoxic potential. Objectives of the present study were to estimate the prevalence of chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) in peripheral lymphocytes of pediatric patients on nitrofurantoin (15 children) or furagin (16 children) therapy. Their ages ranged from 0.3 to 13, with a mean of 6.2 years. The mean blood urea and creatinine levels of all patients were within normal range. Cytogenetic analyses were performed prior to the start of therapy, after 1, 6 and 12 months of treatment. The treatment consisted of oral administration of drugs in doses of 1-2 mg/kg per day. No increase in the aberration rate over the level in controls (i.e., the same patients prior to the start of therapy) was observed after different steps of therapy in all patients under study. Statistical analysis did not show any significant differences between the mean SCE rates of nitrofurantoin-treated (maximum 6.99 SCE/cell frequency was determined after 1 month treatment) and controls (6.56 SCE/cell), indicating a lack of genotoxic potential of nitrofurantoin within the therapeutic dose range. However, significantly increased frequencies of SCEs were determined in patients on furagin therapy. No correlation was observed between the SCE rates and duration of therapy. Mean frequencies of SCEs after 1, 6 and 12 months of treatment were 8.14, 7.98 and 8.66 SCE/cell. The results of this study advocate cautious use of furagin in the management of UTI. Long-term low-dose nitrofurantoin therapy does not seem to have genotoxic effect as expressed by induction of SCEs and chromosome aberrations on its pediatric users.