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The aim, in conservative management of vesico-ureteric reflux by antimicrobial prophylaxis, is to prevent recurrent febrile urinary tract infections and consequent renal scarring. However, the effects of this prophylactic strategy are difficult to evaluate, since the required studies comparing children on prophylaxis with controls (without prophylaxis but under careful supervision) are lacking. Furthermore, the optimal length of prophylaxis needs to be defined. Since risk of renal scarring is believed to occur more frequently in young people, and since recurrent urinary infections mainly affect girls, the age and sex of subjects are important in the design of a prophylactic regimen. Nitrofurantoin and trimethoprim are the most common agents used for long-term, low-dose antibacterial prophylaxis. Break-through infections still result from non-compliance and from development of bacterial resistance, the latter mainly arising with trimethoprim. Few studies of prophylactic drugs are available that adequately define patient materials and include a random allocation to the different agents. Further studies of the effects of alternative prophylactic agents are called for, preferably combined with fresh insight into the ecological impact on the bowel and periurethral floras.

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The objective of this study was to evaluate the basis for diagnosis and assessment of children <2 y of age with urinary tract infections (UTI) and to describe their subsequent management as currently practised in Sweden. The study was a prospective, multicentre project as part of a programme for quality assurance. A total of 2309 children (1111M, 1198F) was studied during a 2-y period. Of the population at risk, 1.6% of both boys and girls were diagnosed with a UTI. This represents a minimum figure. Suprapubic bladder aspiration was mainly used during the first year of life, with the highest frequency in the youngest infants. Adhesive bags were used in half of the children, and the frequency increased with age. Imaging of the urinary tract was performed in 97% of the children. Vesicoureteric reflux was the most common finding, occurring in 36% of the girls and 24% of the boys. The presence of dilatation of the upper urinary tract correlated significantly to the presence and grade of reflux. Initial intravenous therapy was given to 31% of the children and long-term antibacterial prophylaxis to 20%. Major differences were found between centres in diagnostic rate, urine sampling technique and the use of parenteral therapy. In conclusion, this study showed a high diagnostic rate of urinary infections in children below 2 y of age. The urine sampling technique was optimal (suprapubic aspiration) in half of the infants, but less reliable in the children above 1 y of age. The frequency of imaging investigations of the urinary tract was high. The strategies for diagnosis and treatment varied considerably among centres.

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The efficacy of single dose treatment with trimethoprim compared to a 5-day course with the same drug was investigated in 100 children, 3-12 years, with isolated episodes of symptomatic non-febrile urinary tract infection. Cure, defined as sterile urine during the first week after treatment, was achieved in 74% (37/50) in the single dose group compared to 86% (43/50) in the 5-day treatment group. The difference was not statistically significant (chi 2 = 2.25, p = 0.134 two-tailed). The cure rates in relation to P-fimbriation of the infecting E. coli strains were similar in the two groups. During the 6 month follow-up, six children in each treatment group had one or more reinfections. Extended studies are needed to conclude if single dose and conventional treatment courses are equally effective.

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The periurethral flora was examined in 18 girls by use of a quantitative sampling method before, during, and three weeks after treatment with antibiotics for upper respiratory tract infections. Eight girls received amoxicillin. In five of them the anaerobic flora showed a reduction in total counts and in numbers of different species, and all eight girls got a heavy colonisation with enterobacteria during treatment. Three weeks after treatment the anaerobic and aerobic flora had reversed to the pretreatment composition. In 10 girls treated with trimethoprim-sulphamethoxazole the anaerobic flora remained unaffected and no enterobacterial overgrowth was registered during the study period. We propose that antibiotics could be one among several factors involved in the pathogenesis of urinary tract infection, by suppression of the anaerobic microflora and promotion of the colonisation with enterobacteria.

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The in vitro susceptibility of sixty-four isolates of periurethral anaerobic bacteria to nine commonly used antibiotics was analyzed. Using a quantitative sampling method, the three predominant anaerobic strains were isolated from each periurethral sample of twenty-one healthy prepubertal girls. The majority of strains showed high sensitivity to ampicillin and phenoxymethylpenicillin, whereas trimethoprim and trimethoprim--sulfamethoxazole showed no or only slight inhibition of growth of most strains. Intermediate sensitivity was found to erythromycin, cefuroxime, pivmecillinam, norfloxacin and nitrofurantoin. Our data suggest that several antibiotics used in paediatric praxis might influence the indigenous periurethral anaerobic microflora. Hypothetically, this may be a factor of importance in the pathogenesis of ascending urinary tract infections.

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Residual urine was assessed by ultrasound in children with single attacks of symptomatic lower urinary tract infection and in healthy controls. Residual urine was found significantly more often in the 39 patients during acute illness as well as during a follow-up of 6 months, compared to 55 control children. Infections caused by P-fimbriated Escherichia coli were not more often associated with residual urine than infections with nonP-fimbriated Escherichia coli or other bacterial species. It is suggested that residual urine is a facilitating host factor among others in the pathogenesis of symptomatic urinary tract infection in childhood.

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Retrospective studies suggest that circumcision of newborn boys will reduce the frequency of male early infantile urinary tract infection (UTI) by about 90%. If they are correct, this will be the first known instance of a common potentially lethal disease being preventable by extirpation of a piece of normal tissue. To reconcile the phenomenon with existing views of evolution and biology, it is suggested that the effects of one unphysiological intervention are counterbalancing those of another--ie, colonisation of the baby's gastrointestinal tract and genitals in maternity units by Escherichia coli strains of non-maternal origin, to which the baby has no passive immunity. As an alternative to circumcision to prevent early infantile male UTI, more natural colonisation could be promoted by strict rooming-in of mother and baby or by active colonisation of the baby with his mother's anaerobic gut flora.

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P-fimbriation of Escherichia coli is an important factor in the pathogenesis of childhood pyelonephritis. The present study investigates children with single episodes of symptomatic non-febrile urinary tract infection, i.e. cystitis, with respect to clinical appearance and bacteriology, especially the frequency of P-fimbriated E. coli. The study included 75 children, 57 of whom had their first attack of urinary tract infection. E. coli was the causative agent in 88% (66/75) of the infections, and 48% (32/66) of E. coli strains were P-fimbriated. No association was found between identification of P-fimbriated E. coli at index infection and proneness to reinfection during the following six-month period. It is suggested that P-fimbriated E. coli is a virulence factor even in lower urinary tract infections, when occurring in single, symptomatic episodes.

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We describe a male infant with psychomotor retardation and leukodystrophy who excretes large quantities of N-acetylaspartate in his urine. A high CSF/plasma concentration ratio of N-acetylaspartate indicates that this substance originates in the brain. Fibroblasts from the patient are deficient in aspartoacylase activity. It is proposed that the dysmyelination in the patient may be due to failure of N-acetylaspartate to serve as a carrier of acetyl groups from mitochondria to the cytosol for lipogenesis.

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We report 6 children who showed clinical symptoms and laboratory signs of acute pyelonephritis but in whom bacteriuria was insignificant, with Escherichia coli 10(4)/ml, or less. None of the children had symptoms of other disease. Three of the children who were at first treated inadequately or were not treated with antibiotics developed significant bacteriuria later on (10(5)/ml, or greater). Ultrasonic scanning to evaluate kidney involvement at the acute phase of disease showed transient changes in four of the 6 children--dilatation of one or both pelves or increased ecogenicity of the renal sinus, or both. The urinary E coli strains isolated from all 6 children were P-fimbriated, as determined by a P-fimbriae specific particle agglutination test (PPA test). P-fimbriate E coli are known to be strongly associated with acute non-obstructive pyelonephritis in children and we suggest that the finding of any number of P-fimbriated E coli in the urine of children with clinical evidence of acute pyelonephritis supports this clinical diagnosis.

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The periurethral anaerobic and aerobic microfloras were investigated in 18 healthy premenarcheal girls, 5 to 14 years of age, by using a quantitative sampling method. Colonization of the female periurethral area with enterobacteria seems to be an important step in the development of urinary tract infections, and the present study was undertaken as a stage in elucidating factors that might control the establishment of urinary tract pathogens periurethrally. The study showed that obligate anaerobic bacteria constituted 95.0% (standard error, +/- 5.8%) of the total colony-forming units per square centimeter of periurethral area. An average of 7.0 different anaerobic and 2.7 different aerobic strains per specimen was obtained. The flora was dominated by anaerobic gram-positive cocci and gram-positive rods, whereas anaerobic gram-negative rods comprised a minor part. The most commonly encountered anaerobic isolates were peptococci and peptostreptococci, propionibacteria, bifidobacteria, eubacteria, and bacteroides in decreasing order of frequency. The aerobic flora consisted most commonly of nonhemolytic streptococci and diphtheroids. The findings suggest that the periurethral microenvironment is a distinctive ecological niche, separate from the fecal and skin biotas, although it has some characteristics in common with the vaginal flora.

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Seventy-two pregnant and 88 non-pregnant women were examined to see whether the periurethral region had been colonised with group B streptococci (Streptococcus agalactiae), enterococci, and Gram-negative rods belonging to the Enterobacteriaeceae. A semi-quantitative method was used for periurethral sampling, and paired urethral swabs were also collected to compare the isolation rates of group B streptococci from the two sites and with the two sampling methods. A higher isolation rate was found with periurethral sampling. Most specimens showed no or scanty growth of Gram-negative rods. Pregnancy was often associated with heavy growth of enterococci. Sampling performed during menstruation and while oral contraceptives were being used produced high isolation rates of group B streptococci. These results seem to suggest that the periurethral area might protect against genital colonisation with group B streptococci as it does against urinary tract infection and that hormonal factors influence the carriage of these organisms.

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The present study was undertaken to provide information about the presence of bacterial flora in the periurethral region of healthy children and its variation with age and sex. It was intended as a basis for subsequent studies in individuals prone to urinary tract infection. Quantitative methods were used for bacteria sampling and culture. The study included 394 girls and 305 boys from birth to 16 years. During the first few weeks of life a massive aerobic bacterial flora (E. coli, enterococci, staphylococci) was established in the periurethral region of both sexes. The colonization with E. coli and enterococci began to diminish already during the first year of life and became very scanty after the age of 5 years. In newborns E. coli colonization was dense in boys and scanty in girls. Later E. coli was the dominating gram-negative species in girls of all age groups. In boys E. coli dominated during the first half year of life, later Proteus was as common as E. coli; staphylococci did not change very much. Urine samples from healthy school-children contained very few gram-negative bacteria; even when collected without preceding cleansing. The results suggest that there might be a local defence mechanism maturing during the first year of life, eventually protecting the exposed area from colonization with gram-negatives and enterococci.

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After the age of 5 years, normal children have but few aerobic gram-negative rods periurethrally. This study examines whether there is an abnormal periurethral colonization in urinary tract infection-prone girls during infection-free intervals, indicating a defective local defence. In 13 girls with a history of recurrent infection, daily bacterial samples were obtained from the periurethral area and from urine. Sampling continued until an infection eventually occurred. Seven girls contracted a urinary tract infection within 3-30 days. All were heavy colonized with gram-negative rods, often several species, before infection appeared. Serotyping of E. coli confirmed that it was the colonizing strain which later invaded the bladder. The findings suggest a local defect in the antibacterial defence of infection-prone individuals and gives strong evidence for ascending infection. Six girls remained uninfected during an observation period of 9-123 days. They all had a normal periurethral flora. A reasonable hypothesis would be that the same factor counteracted colonization and infection. Since abnormal periurethral colonization was not a constant phenomenon the postulated defect may vary. This might explain the fact that urinary tract infections often appear in quick succession, often followed by long infection-free intervals.

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