[Long-term Cefadroxil prophylaxis in children with recurrent urinary tract infections]. [Prophylaxis of recurrent urinary tract infections in children. Results of an open, controlled and randomized study about the efficacy and tolerance of cefixime compared to nitrofurantoin]. Controlled trial of prophylactic treatment in childhood urinary-tract infection. Antibiotic prophylaxis and recurrent urinary tract infection in children. Prevention of recurrent urinary tract infections in girls. Duration of treatment for urinary tract infections in children. Comparison of trimethoprim-sulfamethoxazole, cephadroxil and cefprozil as prophylaxis for recurrent urinary tract infections in children. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Comparison of long-term, low-dose pivmecillinam and nitrofurantoin in the control of recurrent urinary tract infection in children. An open, randomized, cross-over study. Nitrofurantoin versus trimethoprim prophylaxis in recurrent urinary tract infection in children. A randomized, double-blind study.
The aim of the study was to evaluate the efficacy and safety of low-dose, long-term cefadroxil prophylaxis in preventing recurrent urinary tract infections in children. A prospective, randomized trial in 33 children (32 female, 1 male) aged 2-14 years (mean 8.1+/-2.8) was conducted. Children with recurrent urinary tract infections were commenced to six-month prophylaxis with cefadroxil at the dosage of 12.5-15.0 mg/kg at bedtime administered every night (group I, n=15) or alternate night (group II, n=18). Escherichia coli was the most frequently isolated agent (90.9%), followed by Proteus mirabilis (3.0%) and Klebsiella oxytoca (3.0%) and Staphylococcus epidermidis (3.0%). Cefadroxil prophylaxis was effective in 80% of patients in group I and in 78% patients in group II. Reinfection occurred in 3/15 (20%) patients in-group I and in 4/18 (22.2%) patients in-group II (odds ratio--1.14; 95% confidence interval--0.16-8.3). The difference of reinfection rate between the groups was not significant (p=0.88). The rate of day- and night-time wetting in both groups before prophylaxis of urinary tract infections was high. It decreased significantly at the end of prophylactic treatment with cefadroxil (from 42.4% to 9.1% and from 39.4% to 6.1% respectively). Mild adverse reaction (nausea) was observed in 1/33 patient. In conclusion our study shows that cefadroxil is an effective, well-tolerated and safe agent in the urinary tract infections prophylaxis. Prophylaxis of recurrent urinary tract infections in children with cefadroxil on alternate night regimen might reduce the cost of the treatment. Urinary tract infections are quite frequent in children. Urinary tract obstruction combined with recurrent urinary tract infections increase the risk for renal impairment. Therefore prophylaxis of reinfection is an important nephroprotective procedure. The aim of this open, controlled, randomised pilot study was to compare the efficacy and tolerance of a low dose prophylaxis with Cefixime versus Nitrofurantoin. 60 girls aged 1 to 11 years with at least 2 urinary tract infections within the preceding year were included in the study. The minimum duration of therapy was 6 months and was extended to 12 months for most of the children. The number of recurrent infections was the main criteria for efficacy evaluation, whereas adverse events were analysed to evaluate tolerance. Statistical significant differences between the two treatment groups, regarding recurrence rates could not be demonstrated. Tolerance was comparable in both groups. The influence on gut flora of cefixime given as a low dose regimen over a long period of time corresponds with already published results and was not correlated with a higher number of gastrointestinal side effects.
                Low-dose Cefixime (2 mg/kg bodyweight) is effective and well tolerated in the prophylaxis of recurrent urinary tract infections. Efficacy and tolerance of cefixime were comparable to the results obtained with nitrofurantoin. Due to the small number of patients this study was only a pilot study. Low-dose cefixime, however, could become an alternative to standard regimens in the prophylaxis of recurrent urinary tract infections. This should be investigated in further studies. nan Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children.
                We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data.
                From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions).
                Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.)
                2009 Massachusetts Medical Society Eighteen girls between the ages of 3 and 13 years--with a history of at least three culture-documented episodes of bacteriuria in the previous year, but without radiologic evidence of major urinary tract abnormality--were placed on a double-blind, crossover study comparing the effectiveness of nitrofurantoin macrocrystals against a placebo in preventing the recurrence of bacteriuria. Each child was placed on a daily low dose of nitrofurantoin (1.2 to 2.4 mg/kg/day) or an identical-appearing placebo for six months. Each child was then placed on the opposite capsule for a similar period. There were 35 episodes of bacteriuria (4.2 episodes/patient/yr) in the patients taking the placebo, which compared with a rate of 3.8 episodes/patient/yr during the year prior to the study. Only two episodes (0.2 episodes/patient/yr) occurred in the patients taking the drug. The difference in the rate of recurrent bacteriuria between the girls on placebo and on medication is significant at the 0.01 level using the Wilcoxin matched-pairs test. There were no adverse reactions to the drug. Nitrofurantoin macrocrystals in a single daily low dose appear to be a safe, effective method of preventing recurrent bacteriuria in girls at high risk. In a double-blind trial 45 children aged 6 months to 14 years with Escherichia coli infections of the urinary tract were given co-trimoxazole for two weeks and then allotted at random to one of two treatment groups for the remainder of six months; one continued with the active drug and the other with dummy tablets of identical appearance. Of the 24 children who took co-trimoxazole for two weeks and the 21 who took it for six months, 11 and 10, respectively, remained without further infections for at least a year. Over 90% of the reinfections occurred within five months of stopping the antibiotics, and the longer treatment did not cause any delay in their appearance. Thus probably a six-month course of treatment is no more likely to achieve a cure than a two-week course; nevertheless, no infection occurred during treatment, and there may be an advantage in continuing with antibiotics in small dosage. The aim of this study was to compare the efficacy of prophylactic trimethoprim-sulfamethoxazole (TMP/SMZ), cefprozil and cephadroxil treatments in children who have recurrent urinary tract infection, but no urinary tract pathology. After acute urinary tract infections (UTIs) were treated, the patients were divided into 3 groups randomly and TMP/SMZ was given to 21 patients, cephadroxil was given to 25 patients and cefprozil was given to 34 patients for 3 months--one dose at night. All patients were followed for 6 months following prophylaxis. The frequency of symptomatic UTIs among groups during prophylaxis was not statistically different, however the number of symptomatic UTIs in the cephadroxil group was lower than the other groups. Asymptomatic bacteriuria episodes were detected in TMP/SMZ and cefprozil groups, whereas no asymptomatic bacteriuria episodes were seen in the cephadroxil group. The number of patients with symptomatic UTI during the follow-up period was not different between groups, however all the asymptomatic bacteriuria episodes were encountered in the cefprozil group. In conclusion, in this study cephadroxil was found to be slightly superior to TMP/SMZ and cefprozil in preventing asymptomatic bacteriuria episodes and symptomatic UTIs in children with recurrent UTI and normal urinary tract system. Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection.
                The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months.
                Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor.
                For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode. Thirty-five children with a history of vesicoureteric reflux or with recurrent urinary tract infections were randomly allocated to low-dose prophylactic treatment with pivmecillinam or nitrofurantoin. After 6-10 months they were crossed over to the alternate drug for another 6 months, but only 24 completed the study because of lack of compliance or intolerance to nitrofurantoin. There was no significant difference in the long-term prophylactic effect between the two drugs, the overall infection rate being 0.7/patient-year. Pivmecillinam was significantly better tolerated than nitrofurantoin (P = 0.01). Nitrofurantoin effected no major change in the faecal flora, and nearly all urinary infections occurring during long-term treatment were caused by Escherichia coli. In contrast, a marked reduction of E. coli and a marked increase in Gram-positive cocci were found in the faecal flora during treatment with pivmecillinam. Seventy per cent of infections were caused by Streptococcus faecalis and only 20% by E. coli during pivmecillinam treatment (P = 0.001). The efficiency of nitrofurantoin and trimethoprim prophylaxis in preventing recurrent urinary tract infections (UTI) was compared by means of actuarial percentage recurrence-free curves in a randomized, double blind study in 130 children (126 girls, 4 boys) aged 1 to 14 years (mean 7.5). The children received the antibiotics for 6 months. Nitrofurantoin proved to be the most efficient prophylactic drug in patients with abnormal urography and/or reflux (n = 60) as evaluated by actuarial percentage recurrence-free analysis (p = 0.0025). However, no differences was found in patients without urinary tract abnormalities. Nitrofurantoin prophylaxis altered neither the pattern of resistance nor the bacteriological constellation, while patients receiving trimethoprim prophylaxis had 76% trimethoprim resistant bacteria during prophylaxis, compared with 8% before (p less than 0.0001) and 17% after (p less than 0.0001) prophylaxis. The percentage of recurrences due to E. coli (70-80%) was unaffected by trimethoprim prophylaxis, but the proportion due to trimethoprim resistant E. coli was significantly higher during prophylaxis (65%) than before (6%, p less than 0.0001) and after (11%, p less than 0.001). The percentage of Staphylococcus epidermidis UTI was significantly higher during trimethoprim prophylaxis (27%) than before (2%, p less than 0.0003). Following prophylaxis there was no difference in the actuarial percentage recurrence-free curves of the two regimens. Side effects occurred more frequently in the nitrofurantoin group (37%) than in the trimethoprim group (21%) (p = 0.05). The majority of side effects in the nitrofurantoin group derived from gastrointestinal symptoms. In conclusion, nitrofurantoin is recommended as the first choice prophylactic treatment of children with recurrent UTI and urinary tract abnormalities.
Long-term antibiotics appear to reduce the risk of repeat symptomatic UTI in susceptible children but the benefit is small and must be considered together with the increased risk of microbial resistance.