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Antibiotic prophylaxis in children with relapsing urinary tract infections: review.

Recurrent urinary tract infections (UTIs) are observed in 30-50% of children after the first UTI. Of these, approximately 90% occur within 3 months of the initial episode. The basic aim of antibiotic prophylaxis in children with malformative uropathy and/or recurrent UTIs, is to reduce the frequency of UTIs. The bacteria most frequently responsible for UTI are gram-negative organisms, with Escherichia coli accounting for 80% of urinary tract pathogens. In children with recurrent UTIs and in those treated with antibiotic prophylaxis there is a greater incidence of UTI due to Proteus spp., Klebsiella spp. and Enterobacter spp., whereas Pseudomonas spp., Serratia spp. and Candida spp. are more frequent in children with urogenital abnormalities and/or undergoing invasive instrumental investigations. Several factors are involved in the pathogenesis of UTI, the main ones being circumcision, periurethral flora, micturition disorders, bowel disorders, local factors and hygienic measures. Several factors facilitate UTI relapse: malformative uropathies, particularly of the obstructive type; vesico-ureteric reflux (VUR); previous repeated episodes of cystitis and/or pyelonephritis (3 or more episodes a year), even in the absence of urinary tract abnormalities; a frequently catheterized neurogenic bladder; kidney transplant. The precise mechanism of action of low-dose antibiotics is not yet fully known. The characteristics of the ideal prophylactic agent are presented in this review, as well as indications, dosages, side effects, clinical data of all molecules. While inappropriate use of antibiotic prophylaxis encourages the emergence of microbial resistance, its proper use may be of great value in clinical practice, by reducing the frequency and clinical expression of UTIs and, in some cases such as VUR, significantly helping to resolve the underlying pathology.

Anti-Infective Agents↗

Technical report: urinary tract infections in febrile infants and young children. The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement.

OVERVIEW: The Urinary Tract Subcommittee of the American Academy of Pediatrics Committee on Quality Improvement has analyzed alternative strategies for the diagnosis and management of urinary tract infection (UTI) in children. The target population is limited to children between 2 months and 2 years of age who are examined because of fever without an obvious cause. Diagnosis and management of UTI in this group are especially challenging for these three reasons: 1) the manifestation of UTI tends to be nonspecific, and cases may be missed easily; 2) clean voided midstream urine specimens rarely can be obtained, leaving only urine collection methods that are invasive (transurethral catheterization or bladder tap) or result in nonspecific test results (bag urine); and 3) a substantial number of infants with UTI also may have structural or functional abnormalities of the urinary tract that put them at risk for ongoing renal damage, hypertension, and end-stage renal disease (ESRD). METHODS: To examine alternative management strategies for UTI in infants, a conceptual model of the steps in diagnosis and management of UTI was developed. The model was expanded into a decision tree. Probabilities for branch points in the decision tree were obtained by review of the literature on childhood UTI. Data were extracted on standardized forms. Cost data were obtained by literature review and from hospital billing data. The data were collated into evidence tables. Analysis of the decision tree was used to produce risk tables and incremental cost-effectiveness ratios for alternative strategies. RESULTS: Based on the results of this analysis and, when necessary, consensus opinion, the Committee developed recommendations for the management of UTI in this population. This document provides the evidence the Subcommittee used in the development of its recommendations. CONCLUSIONS: The Subcommittee agreed that the objective of the practice parameter would be to minimize the risk of chronic renal damage within reasonable economic constraints. Steps involved in achieving these objectives are: 1) identifying UTI; 2) short-term treatment of UTI; and 3) evaluation for urinary tract abnormalities.

Child, Preschool↗

Jaundice as an early diagnostic sign of urinary tract infection in infancy.

OBJECTIVE: Urinary tract infections (UTIs) are a common clinical problem in febrile infants younger than 8 weeks old, with a prevalence between 5% and 11%. Previous studies have noted that jaundice may be one of the first signs of a bacterial infection in infants. Our goal was to determine the incidence of UTIs in asymptomatic, jaundiced infants younger than 8 weeks old and to determine which historical and laboratory parameters are associated with UTIs. METHODS: We prospectively evaluated asymptomatic, jaundiced infants younger than 8 weeks old for evidence of a UTI (defined as >10 000 colony-forming units per milliliter of a single pathogen, obtained by bladder catheterization). A serum fractionated bilirubin level was obtained on all study patients. Detailed questionnaires were completed, which included demographic information, prenatal, intrapartum, and postnatal events. RESULTS: Twelve (7.5%) of 160 infants had a UTI (95% confidence interval: 3.9%-12.7%). Isolated organisms included Escherichia coli, Enterobacter cloacae, Enterococcus, Klebsiella pneumoniae, group B Streptococcus, Streptococcus viridans, and Staphylococcus aureus. Patients with the onset of jaundice after 8 days of age had a higher incidence of UTI, 6 (50%) of 12 infants in the positive culture group, versus 15 (10%) of 148 infants in the negative culture group. Abnormal urinalysis and microscopy results were noted in 5 (42%) of 12 infants with a UTI, and 6 (55%) of 11 infants had abnormal renal ultrasound results. CONCLUSION: A UTI was found in 7.5% of asymptomatic, afebrile, jaundiced infants younger than 8 weeks old. In addition, infants with the onset of jaundice after 8 days of age or patients with an elevated conjugated bilirubin fraction were more likely to have a UTI. Therefore, we recommend that testing for a UTI be included as part of the evaluation in asymptomatic, jaundiced infants presenting to the emergency department.

Age Factors↗

Epidemiology of urinary tract infection: II. Diet, clothing, and urination habits.

Although several health habits and behaviors are commonly cited in medical and nursing textbooks as potential causes of urinary tract infection (UTI) in women, few have been studied in a systematic fashion. In a case-control study, we evaluated the associations between UTI and the most commonly mentioned risk factors: urination habits, diet, clothing, and soaps. Because sexual intercourse and diaphragm use increase the risk of UTI, we assessed the effect of health habits and behaviors controlling for these two risk factors. Women with initial UTI were compared with controls with no UTI history; women with a second UTI were compared to those with initial UTI. For the 25 initial cases, 19 secondary cases, and 181 controls enrolled in the study from a university health service, we found using tampons and drinking soft drinks to be moderately associated (RR greater than or equal to 1.4) with both initial and recurrent UTI. Although several other individual habits had only small associations with UTI, several of these behaviors together might substantially increase risk of initial or recurring UTI.

Adolescent↗

Urinary tract infections in patients with spinal cord lesions: treatment and prevention.

Even though the mortality due to urinary tract complications has decreased dramatically during the last decades in individuals with spinal cord lesions (SCL), urinary tract infections (UTI) still cause significant morbidity in this population. Complicated UTI are caused by a much wider variety of organisms in individuals with SCL than in the general population and are often polymicrobial. Escherichia coli, Pseudomonas spp., Klebsiella spp., Proteus spp., Serratia spp., Providencia spp., enterococci, and staphylococci are the most frequently isolated bacteria in urine specimens taken from individuals with SCL. There is no doubt that the greatest risk for complicated UTI in these individuals is the use of an indwelling catheter. Intermittent catheterisation during the rehabilitation phase has been shown to lower the rate of UTI, and virtually eliminate many of the complications associated with indwelling catheters. Persons with SCL should only be treated for bacteriuria if they have symptoms. Generally, it is advisable to use antibacterial agents with little or no impact on the normal flora. Single agent therapy - in accordance with antimicrobial susceptibility test - is preferred. We advise extending treatment to at least 5 days, and in those with reinfection or relapsing UTI, at least 7 to 14 days, depending on the severity of the infection. The diagnosis of structural and/or functional risk factors is essential in order to plan an optimal treatment for UTI in individuals with SCL, which should include treatment of simultaneously occurring predisposing factors. The treatment of structural risk factors follows general urological principles, aiming for sufficient outlet from the bladder with minimal residual urine and low pressure voiding. For prevention of UTI, general cleanliness and local hygiene should be encouraged. If the patient has a reinfection or relapsing symptomatic UTI, it is important to check for inadequately treated infection and complications, which need special attention, in particular residual urine and urinary stones. No reliable evidence exists of the effectiveness of cranberry juice and other cranberry products. Prophylactic antibacterials should only be used in patients with recurrent UTI where no underlying cause can be found and managed, and in particular if the upper urinary tract is dilated. Antibacterials should not be used for the prevention of UTI in individuals with SCL and indwelling catheters. However, the use of prophylactic antibacterials for individuals with SCL using intermittent catheterisation or other methods of bladder emptying is controversial.

Anti-Bacterial Agents↗

Bacterial adherence and humoral immune response in women with symptomatic and asymptomatic urinary tract infection.

PURPOSE: To determine the role of humoral immune response and bacterial adherence in the pathogenesis of symptomatic and asymptomatic urinary tract infection in women. METHODS: The study population consisted of 30 women with symptomatic UTI, 30 women with asymptomatic UTI and 30 healthy women as controls. Bacterial adherence to vaginal epithelial cells was studied and the concentration of serum and urine antibodies to mixed coliform antigen and clinical isolate was determined by ELISA. Surface hydrophobicity of the urine isolates was determined. Student's unpaired t test and Pearson's correlation coefficient test were used in the statistical analysis. RESULTS: Compared to asymptomatic UTI, significantly more number of bacteria adhered to the epithelial cells of women with symptomatic UTI (P< 0.001). All cases of UTI had significantly high concentration of urinary IgG antibody to mixed coliform antigens. Asymptomatic UTI cases had higher concentrations of urinary IgG, IgM and IgA antibodies to clinical isolate. Concentration of sIgA level was more in symptomatic UTI. Significant correlation was observed between urinary IgG and adherence of clinical isolate in case of asymptomatic UTI. CONCLUSIONS: The present study showed that greater receptivity of epithelial cells to bacteria may increase the susceptibility to UTI. Humoral immune response and local immunity may modify the pathogenesis of UTI.

Adolescent↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). II. Background of patients].

Clinical background was investigated on 916 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period from June to November, 1988. 1. Distribution of sexes, ages and infections: Among males, fifties and older were most frequent and most of them had complicated UTIs. Among females, most cases among twenties or thirties were uncomplicated UTIs. Forties and older cases were most frequent and complicated UTIs were more frequent among them than among patients in twenties and thirties. 2. Distribution of sexes, ages and pathogens isolated from UTIs: In males, Pseudomonas spp. and Enterococcus spp. were frequently isolated. In contrast, in females, Escherichia coli was the most frequent. In thirties, E. coli was not the most frequently isolated bacterium. Frequency of Pseudomonas spp., other non-fermented Gram-negative rods and Enterococcus spp. were greater among patients with higher ages. 3. Administration of antibiotics and pathogens isolated from UTIs: (1) Before administration: In uncomplicated UTIs, E. coli accounted for the majority of causative organisms. In complicated UTIs, particularly in those cases with indwelling catheter, Enterococcus spp. and Pseudomonas spp. were rather frequently isolated. (2) After administration: In complicated UTIs, higher number of pathogens were isolated. Pseudomonas spp. and Enterococcus spp. were the most frequent. Distribution of pathogens isolated from complicated UTIs without indwelling catheter was similar to that before antibiotic administration.

Adult↗

Current concepts in urinary tract infections.

Urinary tract infections (UTIs) are common infectious diseases that can be associated with substantial morbidity and significant expenditures. This review highlights the current concepts and recent advances in our understanding and management of this condition. Specific topics include pathogenesis, host factors, antimicrobial resistance, recurrent UTIs in women, diagnosis, treatment of uncomplicated and complicated UTIs, prophylaxis, catheter associated bacteriuria, pregnancy, diabetes, UTIs in men, prostatitis, and the chronic pelvic pain syndrome. UTIs can be viewed as an interaction between specific bacterial virulence factors and the patient. A new model explaining the pathogenesis of recurrent UTIs has been presented. There is a need to reconsider traditional treatment recommendations in the face of local resistance patterns, as well as the need to make better use of drugs that are currently available. Prospects for prevention of recurrent UTI include natural compounds, bacterial interference and immunization. With regard to UTI risk in women, patients can be classified based on age, and functional and hormonal status. Appropriate treatment approaches must be based on this classification. In contrast to uncomplicated UTIs, management of most complicated infections depends on clinical experience and resources at individual institutions rather than on evidence based guidelines. Asymptomatic bacteriuria generally should not be treated except in high-risk catheterized patients and in pregnancy. UTIs in men generally require formal urologic evaluation. Our understanding of the etiologies, diagnostic strategies, and treatment options for prostatitis and the chronic pelvic pain syndrome in men continues to evolve.

Abscess↗

[Effects of the administration of urinary trypsin inhibitor on the morphology and function of platelets in the rat septic models].

Effects of urinary trypsin inhibitor (UTI) on the number, morphology and function of platelets under septic state were studied in rat models of cecal ligation and puncture (CLP). At formation of CLP, 5,000 U/kg/h of UTI was serially administered intraperitoneally and blood was sampled after 16 hours. Comparative study among sham-operation group, CLP group, and CLP + UTI group revealed: 1) inhibition of the platelets of platelet counts and appearance of large-sized, active platelets by UTI in the CLP + UTI group, 2) increase of platelet maximum aggregation rate (MAR) by ADP and increase of collagen in the CLP group, while inhibition in the CLP + UTI group and 3) by HPLC evaluation of adenine nucleotide in the platelet, increased levels of total ATP and ADP in the CLP group, particularly, increases of ATP in the metabolic pool and ADP in the granular pool. CLP + UTI group did not show these changes in the adenylate pool. UTI was thus considered to stabilize the platelet cycle in sepsis. Platelets under septic state might be hyperactive, and thrombosis is easy to occur. UTI administration might work for maintaining constancy of the platelet internal environment and improve septic state because adenine nucleotide level in the platelet did not change in the CLP + UTI group through changed in the CLP group.

Adenine Nucleotides↗

[The value of antibody coated bacteria in the evaluation of the level of urinary tract infections].

In 51 female and 43 male patients urinary tract infections (UTI) were detected by urinary cultures. The levels of UTI were detected by clinical and by physical studies, and by laboratory and X ray findings. In 42 of the patients, lower level UTI and in 52 patients upper level UTI were found. In 57.4% of the cases E. coli and in the remainder, proteus, pseudomonas, klebsiella, staphylococci and streptococci were found in decreasing rates as being the etiological agents of UTI. In 20 male and 32 female patients, upper level UTI were found. In the urine sediments of 85% males and 84.3% females with upper level UTI and in 13% males and 11% females with lower level UTI, antibody coated bacteria (ACB) were found to be positive. The difference of ABD in upper and lower level UTI was found to be significant and the detection of ACB by direct fluorescens method in urine sediments was shown to be valuable in the diagnosis of UTI.

Antibody-Coated Bacteria Test, Urinary↗

[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1992). III. Secular changes in susceptibility].

Susceptibilities of Enterococcus faecalis, Staphylococcus aureus, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Proteus mirabilis, Pseudomonas aeruginosa and Serratia spp. isolated from patients with urinary tract infections (UTIs) in 11 hospitals during June 1992 to May 1993 to various antimicrobial agents were compared with those in the same period of previous years according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. The susceptibilities of E. faecalis isolated from uncomplicated UTIs to quinolones has decreased. As for S. aureus, Citrobacter spp., Enterobacter spp., P. mirabilis and Serratia spp., which were detected very few in 1989, 1990, 1991 and 1992, their susceptibilities were not observed an obvious change. E. coli, all strains were highly susceptibilities to latamoxef and cefozopran. And the susceptibilities of E. coli isolated from uncomplicated UTIs and complicated UTIs without indwelling catheter to minocycline has decreased in 1991, but they has been indicated a trend of recovery in 1992. The difference in according UTI's classification of the susceptibilities of Klebsiella spp. to minocycline in 1991 has not recognized in 1992. And the susceptibilities of Klebsiella spp. isolated from complicated UTIs without indwelling catheter to quinolones has decreased. The susceptibilities of P. aeruginosa isolated from complicated UTIs to quinolones has been indicated a trend of recovery. These data should be considered in clinical treatment of various urinary tract infections.

4-Quinolones↗

Urinary trypsin inhibitor efficiently inhibits urokinase production in tumor necrosis factor-stimulated cells.

We demonstrated that urinary trypsin inhibitor (UTI) efficiently inhibits soluble and tumor cell-associated plasmin activity and subsequently inhibits tumor cell invasion and metastasis. The effect of UTI on tumor necrosis factor-alpha (TNF)-induced stimulation of urokinase-type plasminogen activator (uPA) in cultured human umbilical vein endothelial cells (HUVEC) and in the promyeloid leukemia U937 cells was studied. uPA antigen was evaluated in the cell lysate and in the conditioned media by enzyme-linked immunosorbent assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, and Western blot. TNF can promote the production of uPA in HUVEC and in U937 cells. The PKC inhibitors (H7, calphostin C, and staurosporine) inhibited TNF-induced uPA expression and secretion in a dose-dependent manner. Analysis of the expression of cell surface receptor-bound uPA by flow cytometry using uPA-specific MAb indicates that induction of uPA expression by TNF was inhibited when these cells were incubated with UTI. On the other hand, treatment of the cells with UTI alone failed to alter uPA production. UTI also reduced the secretion of uPA in TNF-treated cells. UTI was as effective as PKC inhibitors in inhibiting uPA expression by TNF. Incubation of the cells with UTI, however, had no effect on the ability of PMA to stimulate cell-associated uPA expression. These data suggest that UTI may influence the PKC-dependent protein kinase pathway in uPA expression. The study on intracellular pathways involved in UTI modulation of uPA will enhance our understanding of the role that UTI plays in uPA-mediated cellular invasion.

8-Bromo Cyclic Adenosine Monophosphate↗

Urinary tract infections following renal transplantation.

The incidence of urinary tract infections (UTIs) in 363 adult renal transplant recipients transplanted during the period 1990-96 has been analysed. UTI occurred in 96 patients (26%), most frequently during the first year after transplantation. Female recipients had significantly more UTI than male recipients (49% vs. 14%, p < 0.0001). There was no difference in the incidence of UTI between recipients receiving pig-tail catheters as ureteral stents or not, the figures being 21% vs. 28%, respectively. Age had no influence on the incidence of UTI. In 341 patients treated with cyclosporine the incidence of UTI was 28%, while in 15 patients treated with FK-506 only 1 patient (7%) had a UTI (ns). The majority of organisms cultured were gram-negative (76%), with approximately 1/3 being Escherichia coli and 1/5 being Enterococcus and Klebsiella/Enterobacter. The bacterial spectrum was not influenced by the recipient's age. UTI had no effect on the number of rejections, or on graft and patient survival in living donor transplant recipients. No significant difference was found in graft and patient survival rates at 3 yr between patients who had UTI or no UTI.

Adolescent↗

Risk factors for urinary tract infections in postmenopausal women.

BACKGROUND: Urinary tract infections (UTI) occur frequently in postmenopausal women and account for substantial morbidity and economic costs. Although extensively studied in younger women and older, debilitated women, the risk factors for UTI among healthy community-dwelling postmenopausal women have not been well described. METHODS: We conducted a population-based, case-control study of women aged between 55 and 75 years enrolled in a large, staff-model health maintenance organization. Cases were identified using computerized laboratory and outpatient records. Controls were randomly selected from the plan's enrollment files. We interviewed subjects regarding their habits, general health, and potential risk factors for UTI. RESULTS: We interviewed 899 study subjects and 911 controls. Sociodemographic characteristics were similar in subjects and controls. Most women were insured and white. Like younger women, postmenopausal women with current UTI were more likely to be sexually active (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.07-1.87) and have a history of UTI (OR, 4.20; 95% CI, 3.25-5.42). Like older debilitated women, study subjects were more likely to have diabetes mellitus (OR, 2.78; 95% CI, 1.78-4.35) and to be incontinent (OR, 1.36; 95% CI, 1.03-1.78). Oral estrogen replacement did not reduce UTI risk. CONCLUSIONS: In this population, the risk factors of healthy community-dwelling postmenopausal women reflect the health status of women as they transition toward old age. Sexual activity, history of UTI, treated diabetes, and incontinence were all associated with a higher risk of UTI. The therapeutic role of oral estrogen remains uncertain. Prospective studies in different patient populations are needed to better understand the risk factors of UTI.

Aged↗

Urine testing and urinary tract infections in febrile infants seen in office settings: the Pediatric Research in Office Settings' Febrile Infant Study.

OBJECTIVE: To determine the predictors and results of urine testing of young febrile infants seen in office settings. DESIGN: Prospective cohort study. SETTING: Offices of 573 pediatric practitioners from 219 practices in the American Academy of Pediatrics Pediatric Research in Office Settings' research network. SUBJECTS: A total of 3066 infants 3 months or younger with temperatures of 38 degrees C or higher were evaluated and treated according to the judgment of their practitioners. MAIN OUTCOME MEASURES: Urine testing results, early and late urinary tract infections (UTIs), and UTIs with bacteremia. RESULTS: Fifty-four percent of the infants initially had urine tested, of whom 10% had a UTI. The height of the fever was associated with urine testing and a UTI among those tested (adjusted odds ratio per degree Celsius, 2.2 for both). Younger age, ill appearance, and lack of a fever source were associated with urine testing but not with a UTI, whereas lack of circumcision (adjusted odds ratio, 11.6), female sex (adjusted odds ratio, 5.4), and longer duration of fever (adjusted odds ratio, 1.8 for fever lasting > or = 24 hours) were not associated with urine testing but were associated with a UTI. Bacteremia accompanied the UTI in 10% of the patients, including 17% of those younger than 1 month. Among 807 infants not initially tested or treated with antibiotics, only 2 had a subsequent documented UTI; both did well. CONCLUSIONS: Practitioners order urine tests selectively, focusing on younger and more ill-appearing infants and on those without an apparent fever source. Such selective urine testing, with close follow-up, was associated with few late UTIs in this large study. Urine testing should focus particularly on uncircumcised boys, girls, the youngest and sickest infants, and those with persistent fever.

Adult↗

Long-term antibiotics for preventing recurrent urinary tract infection in children.

BACKGROUND: Acute urinary tract infection (UTI) is common in children. By the age of seven 8.4% of girls and 1.7% of boys will have suffered at least one episode. Symptoms include fever, lethargy, anorexia, and vomiting. UTI is caused by Escherichia coli in over 80% of cases and treatment consists of a course of antibiotics. Due to acute illness caused by UTI and the risk of pyelonephritis-induced permanent kidney damage, many children are given long-term antibiotics aimed at preventing recurrence. OBJECTIVES: To determine the efficacy and harms of long-term antibiotics to prevent recurrent UTI in children. SEARCH STRATEGY: We searched without language restriction MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, the Cochrane Renal Group's Specialised Register, reference lists of review articles and contacted content experts. Date of most recent search: January 2006 SELECTION CRITERIA: Randomised comparisons of antibiotics with other antibiotics, placebo or no treatment to prevent recurrent UTI. DATA COLLECTION AND ANALYSIS: Two authors independently assessed and extracted information. A random-effects model was used to estimate relative risk (RR) and risk difference (RD) for recurrent UTI with 95% confidence intervals (CI). MAIN RESULTS: Eight studies (618 children) were identified, five (406) comparing antibiotics with placebo/no treatment. The duration of antibiotic prophylaxis treatment varied from 10 weeks to 12 months. Compared to placebo/no treatment, antibiotics reduced the risk of repeat positive urine culture (RR 0.44, 95% CI 0.19 to 1.00; RD -30%, 95% CI -56% to -4%) No side effects were reported. One study reported that nitrofurantoin was more effective than trimethoprim in preventing recurrent UTI over a six month period (RR 0.48, 95% CI 0.25 to 0.92; RD -18%, 95% CI -34% to -3%). However, patients receiving nitrofurantoin were more likely to discontinue the antibiotic due to side effects (mainly gastrointestinal) (RR 3.17, 95% CI 1.36 to 7.37; RD 22%, 95% CI 8% to 36%). The other study found cefixime was more effective in preventing recurrent UTI than nitrofurantoin (RR 0.74, 95% CI 0.13 to 4.10; RD -3%, 95% CI -17% to -12%). However, 62% of patients receiving cefixime experienced an adverse reaction during the first six months of treatment (18/29) while only 26% (8/31) of patients receiving nitrofurantoin reported an adverse reaction. AUTHORS' CONCLUSIONS: Large, properly randomised, double blinded studies are needed to determine the efficacy of long-term antibiotics for the prevention of UTI in susceptible children.

Acute Disease↗

Short versus standard duration oral antibiotic therapy for acute urinary tract infection in children.

BACKGROUND: The optimal duration of oral antibiotic therapy for urinary tract infection (UTI) in children has not been determined. A number of studies have compared single dose therapy to standard therapy for UTI, with mixed results. A course of antibiotics longer than a single dose but shorter than the usual 7-10 days might decrease the relapse rate and still provide some of the benefits of a shortened course of antibiotics. OBJECTIVES: The objective of this review was to assess the benefits and harms of short-course (2-4 days) compared to standard duration (7-14 days) oral antibiotic treatment for acute UTI in children. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002) MEDLINE (1966 - September 2002) and EMBASE (1988 -September 2002) without language restriction. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing short-term (2-4 days) with standard (7-14 days) oral antibiotic therapy were selected if they studied children aged three months to 18 years with culture proven UTI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (95% CI). MAIN RESULTS: Ten trials were identified in which 652 children with lower tract UTI were evaluated. There was no significant difference in the frequency of positive urine cultures between the short (2-4 days) and standard duration oral antibiotic therapy (7-14 days) for UTI in children at 0-10 days after treatment (eight studies: RR 1.06; 95% CI 0.64 to 1.76) and at one to 15 months after treatment (10 studies: RR 0.95; 95% CI 0.70 to 1.29). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (one study: RR 0.57, 95% CI 0.32 to 1.01) or in recurrent UTI (three studies: RR 0.39, 95% CI 0.12 to 1.29). REVIEWER'S CONCLUSIONS: A 2-4 day course of oral antibiotics appears to be as effective as 7-14 days in eradicating lower tract UTI in children.

Acute Disease↗

Urinary trypsin inhibitor reduces C-X-C chemokine production in rat liver ischemia/reperfusion.

BACKGROUND AND AIM: Protease inhibitors attenuate ischemia/reperfusion injury. However, the underlying mechanisms by which protease inhibitors prevent reperfusion injury remain obscure. Neutrophils play an important role in reperfusion injury. We studied the effects of urinary trypsin inhibitor (UTI) on production of the C-X-C chemokine, cytokine-induced neutrophil chemoattractant (CINC), by Kupffer cells during ischemia/reperfusion of the liver. METHODS: Liver ischemia was induced in rats by occlusion of the portal vein for 30 min. UTI (50,000 U/kg) was injected intravenously 5 min before vascular clamping. Serum CINC concentrations were measured by enzyme-linked immunosorbent assay. Levels of CINC mRNA in the liver were determined by Northern blot analysis. We also examined the inhibitory effects of UTI on in vitro CINC production by peritoneal macrophages in response to neutrophil elastase (NE). RESULTS: Serum CINC concentrations increased and peaked 6 h after reperfusion. However, pretreatment of animals with UTI blunted this increase in CINC and significantly reduced CINC mRNA levels in the liver after ischemia/reperfusion. UTI also decreased neutrophil accumulation in the liver 24 h after reperfusion. In vitro CINC production by Kupffer cells from rats pretreated with UTI 3 h after ischemia/reperfusion was significantly decreased compared to those from untreated animals. UTI reduced NE activity in vitro in a dose-dependent manner, and UTI significantly reduced in vitro CINC production by peritoneal macrophages stimulated with NE. CONCLUSION: UTI reduces the production of CINC by Kupffer cells stimulated with NE, attenuating ischemia/reperfusion injury of the liver.

Alanine Transaminase↗