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Finden Sie Henriette Richter R Hl Stockfotos in HD und Millionen weiterer redaktioneller Bilder in der Shutterstock-Kollektion. Jeden Tag werden Tausende​. K Grunewald, B Richter, G Meinel, H Herold, RU Syrbe. International Journal of Biodiversity Science, Ecosystem Services , 46, Pixelorientierte. Soziologische Paradigmen: eine Einführung in klassische und moderne Konzepte. R Richter. UTB, 97, When men become fathers: Men's identity at.

Lobel, K. Naber, J. Palou, and P. Tenke] updated the guidelines in several subsequent consensus conferences and added several chapters, one of which deals with catheter-associated UTIs.

EAU guidelines on special forms of urogenital infections, such as sexually transmitted infections 18 , urogenital tuberculosis 19 and urogenital schistosomiasis 20 , have been published elsewhere.

Chapters 12 and 13 of the present guidelines present separate short summaries including a reference link.

For a literature review, PubMed was searched for published meta-analyses, which were used as far as available.

Otherwise, there was a non-structured literature review process by the group members. Each member was responsible for one chapter reporter.

The first draft of each chapter was sent to the committee members asking for comments, which were then considered, discussed and incorporated accordingly.

The formal agreement to each updated chapter was achieved by the EAU working group in a series of meetings. Table 1:Levels of evidence, modified from Sackett et al.

Level Type of evidence 1a Evidence obtained from meta-analysis of randomised trials 1b Evidence obtained from at least one randomised trial 2a Evidence obtained from at least one well-designed controlled study without randomisation 2b Evidence obtained from at least one other type of well-designed quasi-experimental study 3Evidence obtained from well-designed non-experimental studies, such as comparative studies, correlation studies and case reports 4Evidence obtained from expert committee reports or opinions or clinical experience of respected authorities Table 2:Grades of recommendations, modified from Sackett et al.

Grade Nature of recommendations ABased on clinical studies of good quality and consistency addressing the specific recommendations and including at least one randomised trial BBased on well-conducted clinical studies, but without randomised clinical studies C Made despite the absence of directly applicable clinical studies of good quality 1.

Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Resistance trends in urinary tract pathogens and impact on management.

J Urol Oct; 4 Pt 2 Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second year of the SENTRY antimicrobial surveillance program J Antimicrob Chemother Mar;45 3 Nosocomial and community-acquired infections in Germany.

Infection Jul-Aug;25 4 Engineering out the risk for infection with urinary catheters. Emerg Infect Dis Mar-Apr;7 2 Urinary tract infection: economic considerations.

Med Clin North Am Mar;75 2 Bacteriuria and pyelonephritis of pregnancy. Arch Intern Med Feb; DEF 3. Clin Microbiol Infect Sep;6 9 Def 1.

DEF 2. Clin Microbiol Infect Oct;6 10 Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically.

Wayne, PA. The Netherlands, European Association of Urology. Evaluation of new anti-infective drugs for the treatment of urinary tract infection.

General guidelines for the evaluation of new anti-infective drugs for the treatment of UTI. Naber KG. Experience with the new guidelines on evaluation of new anti-infective drugs for the treatment of urinary tract infections.

Int J Antimicrob Agents May;11 ; discussion Guidelines on urinary and male genital tract infections.

In: EAU Guidelines. ISBN EAU guidelines for the management of urinary and male genital tract infections. Eur Urol Nov;40 5 Eur Urol Jul;44 1 EAU guidelines for the management of genitourinary tuberculosis.

Eur Urol Sep;48 3 EAU guidelines for the management of urogenital schistosomiasis. Eur Urol Jun;49 6 Uncomplicated urinary tract infections in adults This chapter is a summary of the ICUD initiative on urogenital infections, sections 5, 6 and 7 on uncomplicated UTIs 1.

These UTIs are seen mostly in women without relevant structural and functional abnormalities within the urinary tract, kidney diseases, and comorbidity that can lead to more serious outcomes and therefore require additional care 2.

Occasionally, other Enterobacteriaceae, such as Proteus mirabilis and Klebsiella spp. Diagnosis 2.

Women who present with atypical symptoms of either acute uncomplicated cystitis or acute uncomplicated pyelonephritis, as well as those who fail to respond to appropriate antimicrobial therapy should be considered for additional diagnostic studies LE:4, GR: B.

According to these principles and the available susceptibility patterns in Europe, fosfomycin trometamol 3 g single dose, pivmecillinam mg for 3 days, and nitrofurantoin macrocrystal mg bid for 5 days, are considered as drugs of first choice in many countries, when available LE: 1a, GR: A.

Alternative antibiotics are ciprofloxacin mg bid, ciprofloxacin extended release mg qd, levofloxacin mg qd, norfloxacin mg bid, and ofloxacin mg bid, each as a 3-day course 16 LE: 1b, GR: B.

However, adverse effects have to be considered Table 2. Table 2. In women whose symptoms do not resolve by the end of treatment, and in those whose symptoms resolve but recur within 2 weeks, urine culture and antimicrobial susceptibility tests should be performed LE: 4, GR: B.

For therapy in this situation, one should assume that the infecting organism is not susceptible to the agent originally used.

Additional investigations, such as an unenhanced helical computed tomography CT , excretory urography, or dimercaptosuccinic acid DMSA scanning, should be considered if the patients remain febrile after 72 h of treatment LE: 4, GR: C.

However, S. A fluoroquinolone for days can be recommended as first-line therapy if the resistance rate of E. If the fluoroquinolone dose is increased, the treatment can probably be reduced to 5 days 22,23 LE: 1b, GR: B.

However, increasing numbers of fluoroquinolone-resistant E. A third-generation oral cephalosporin, such as cefpodoxime proxetil or ceftibuten, could be an alternative 24,25 LE: 1b, GR: B.

However, available studies have demonstrated only equivalent clinical, but not microbiological, efficacy compared with ciprofloxacin. As a result of increasing E.

Co-amoxiclav is not recommended as a drug of first choice for empirical oral therapy of acute pyelonephritis LE: 4, GR: B.

Initial parenteral therapy in severe cases. In women whose pyelonephritis symptoms do not improve within 3 days, or resolve and then recur within 2 weeks, repeated urine culture and antimicrobial susceptibility tests and an appropriate investigation, such as renal ultrasound, CT or renal scintigraphy, should be performed LE: 4, GR: B.

In the patient with no urological abnormality, it should be assumed that the infecting organism is not susceptible to the agent originally used, and an alternative tailored treatment should be considered based on culture results LE: 4, GR: B.

For those patients who relapse with the same pathogen, the diagnosis of uncomplicated pyelonephritis should be reconsidered.

Figure 2. Antimicrobial prophylaxis: Antimicrobial prophylaxis for prevention of recurrent UTI should be considered only after counselling and behavioural modification has been attempted LE: 4, GR: A.

Continuous or postcoital antimicrobial prophylaxis should be considered to prevent recurrent uncomplicated cystitis in women in whom non-antimicrobial measures have been unsuccessful 35 LE: 1a, GR: A.

Drug regimens are shown in Tables 2. Its efficacy in other groups of patients, and its efficacy relative to antimicrobial prophylaxis remain to be established.

For other immunotherapeutic products on the market, larger phase III studies are still missing. Therefore, no recommendations are possible.

Only the specifically in studies tested Lactobacillus strains should be used for prophylaxis. Lactobacillus acidophilus and lactobacillus crispatus CTV05 strains are not available for prophylaxis.

Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC product is available as an orally administered capsule that has been used vaginally but not for UTI prophylaxis 39, Where commercially available, it is reasonable to consider the use of intravaginal probiotics that contain L.

Daily use of the oral product with strains GR-1 and RC is worth testing given that it can restore the vaginal lactobacilli, compete with urogenital pathogens, and prevent bacterial vaginosis, a condition that increases the risk of UTI 40 LE: 1b, GR: C.

The best approach is to use those compounds that have demonstrated clear bioactivity in urine. Recommended antibiotic regimens are shown in Table 2.

When indicated, ultrasonography or magnetic resonance imaging should be used preferentially to avoid radiation risk to the foetus LE: 4, GR: B.

No recommendation can be made with respect to screening for or treatment of bacteriuria in patients with neutropenia LE: 4.

Appendix 1. R elevant clinical trials of antimicrobial therapy of acute uncomplicated cystitis in adult nonpregnant women. Study underpowered to show equivalence Ciprofloxacin SD 1 day Norfloxacin bid 3 days 1b Auquer 67 Ciprofloxacin as effective and tolerable as norfloxacin mg bid for 3 days.

Study underpowered for equivalence. Study underpowered to show equivalence. Fosfomycin trometamol SD 1 day Norfloxacin bid 5 days 1b De Jong 79 Fosfomycin as effective as norfloxacin but had significantly fewer adverse events.

Pefloxacin should be taken with meals to reduce gastrointestinal adverse events. In the abstract, number of patients and dose are missing.

R elevant clinical trials of therapy of acute uncomplicated pyelonephritis. Both treatment regimens after initial IV cefuroxime.

Both treatment regimens after initial IV therapy. Both studies refer to the same cohort. Meropenem 1 g tid?

Side effects more common with 3 weeks treatment 0. Recurrent urinary tract infectionin adult women: diagnosis and treatment. Infect Dis Clin North Am ; Diagnosis and treatment of uncomplicated urinary tract infection.

Eur Urol Nov; 54 5 Management of urinary tract infections in adults. N Engl J Med Oct 28; 18 Collection of urine specimens in general practice: to clean or not to clean?

Outpatient urine culture: does collection technique matter? Arch Intern Med Sep 11; 16 Epidemiology of urinary tract infections: transmission and risk factors, incidence, and costs.

Clinical practice. Acute uncomplicated urinary tract infection in women. N Engl J Med Jul 17; 3 Urinary tract infections. In: Detection, prevention and management.

Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials.

J Infect Jul;64 1 Single-dose treatment of cystitis with fosfomycin trometamol Monuril : analysis of 15 comparative trials on 2, patients.

Giorn It Ost Gin ; Nicolle LE. Pivmecillinam in the treatment of urinary tract infections. J Antimicrob Chemother Sep;46 Suppl ; discussion Short-course nitrofurantoin for the treatment of acute uncomplicated cystitis in women.

Arch Intern Med Nov; 20 Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women.

Clin Infect Dis Oct;29 4 Int J Antimicrob Agents Jun;19 6 Quinolones for uncomplicated acute cystitis in women.

Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults.

Clin Infect Dis Mar;40 5 Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med Jan; 1 Acute Pyelonephritis.

Evaluation of new anti-infective drugs for the treatment of UTI. Clin Infect Di, ; Comparison of ciprofloxacin 7 days and trimethoprim-sulfamethoxazole 14 days for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial.

JAMA Mar; 12 Curr Med Res Opin Nov;23 11 Urology Jan;71 1 Fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute pyelonephritis initially treated with intravenous cefuroxime.

Scand J Infect Dis ;33 5 International, prospective, randomized comparative study versus ciprofloxacin in general practice.

Acute renal infection in women: treatment with trimethoprimsulfamethoxazole or ampicillin for two or six weeks.

A randomized trial. Ann Intern Med Mar; 3 Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology Jul;52 1 Treatment of complicated urinary tract infection in adults: combined analysis of two randomized, double-blind, multicentre trials comparing ertapenem and ceftriaxone followed by an appropriate oral therapy.

J Antimicrob Chemother Jun;53 Suppl 2:ii Empirical monotherapy with meropenem in serious bacterial infections. Meropenem Study Group. Low-dosage cefepime as treatment for serious bacterial infections.

Int J Antimicrob Agents Feb;19 2 Intravenous therapy with doripenem versus levofloxacin with an option to switch to oral therapy for the treatment of complicated lower urinary tract infection and pyelonephritis.

Antimicr Agents Chemotherapy, submitted. Hooton, TM. Recurrent urinary tract infection in women. Int J Antimicrob Agents Apr;17 4 Excretory urography, cystography, and cystoscopy in the evaluation of women with urinary-tract infection: a prospective study.

N Engl J Med Feb; 8 Antibiotics for preventing recurrent urinary tract infection in non-pregnant women. Efficacy and safety of self-start therapy in women with recurrent urinary tract infections.

J Urol Jan; 1 Prevention of recurrent urinary tract infections with immuno-active E. Immunoactive prophylaxis of recurrent urinary tract infections: a meta-analysis.

Int J Antimicrob Agents Feb;33 2 Probiotics prophylaxis in children with persistent primary vesicoureteral reflux.

Pediatr Nephrol Sep;22 9 Clinical study comparing probiotic Lactobacillus GR-1 and RC with metronidazole vaginal gel to treat symptomatic bacterial vaginosis.

Microbes Infect Oct;8 Randomised trial of cranberrylingonberry juice and Lactobacillus GG drink for the prevention of urinary tract infections in women.

BMJ Jun; A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women.

Can J Urol Jun;9 3 Antibiotics for asymptomatic bacteriuria in pregnancy. Treatments for symptomatic urinary tract infections during pregnancy.

Effective prophylaxis for recurrent urinary tract infections during pregnancy. Clin Infect Dis, Apr 14; 4 : Outpatient treatment of pyelonephritis in pregnancy: a randomized controlled trial.

Obstet Gynecol Oct; 86 4 Pt 1 A randomized trial of three antibiotic regimens for the treatment of pyelonephritis in pregnancy. Obstet Gynecol Aug;92 2 Asymptomatic bacteriuria in the elderly.

Urinary tract infection among women aged 40 to behavioral and sexual risk factors. J Clin Epidemiol Jul;54 7 Optimal duration of antibiotic therapy for uncomplicated urinary tract infection in older women: a double-blind randomized controlled trial.

CMAJ Feb; 4 A controlled trial of intravaginal estriol in postmenopausal women with recurrent urinary tract infections.

N Engl J Med Sep; 11 Reduction of bacteriuria and pyuria after ingestion of cranberry juice. JAMA Mar; 10 Urinary tract infections in young men.

In: Bergan T ed. Basel, Switzerland: Karger, vol 1;pp. Ulleryd P. Febrile urinary tract infection in men.

Ciprofloxacin for 2 or 4 weeks in the treatment of febrile urinary tract infection in men: a randomized trial with a 1 year follow-up.

Scand J Infect Dis ;35 1 Reliability of a single urine culture in establishing diagnosis of asymptomatic bacteriuria in adult males. J Clin Microbiol May;9 5 Urine specimen collection with external devices for diagnosis of bacteriuria in elderly incontinent men.

J Clin Microbiol Jun;26 6 Antimicrobial treatment in diabetic women with asymptomatic bacteriuria. N Engl J Med Nov 14; 20 Clinically inapparent asymptomatic bacteriuria in ambulatory elderly men: epidemiological, clinical, and microbiological findings.

J Am Geriatr Soc Nov;38 11 Significance of asymptomatic bacteriuria in neurogenic bladder disease. Urology Apr;23 4 Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo.

Clin Infect Dis Jan;30 1 Urinary tract infections following renal transplantation. Clin Transplant Nov;12 1 Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: a randomized trial.

JAMA Feb; 8 Cefdinir versus cefaclor in the treatment of uncomplicated urinary tract infection. Clin Ther Jul;22 7 Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women.

Antimicrob Agents Chemother Mar;47 3 Cefuroxime axetil versus ofloxacin for short-term therapy of acute uncomplicated lower urinary tract infections in women.

Infection Jan-Feb;21 1 Single-dose ciprofloxacin versus 3 days of norfloxacin in uncomplicated urinary tract infections in women. Clin Microbiol Infect Jan;8 1 Ciprofloxacin Urinary Tract Infection Group.

Am J Med Mar; 3 A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection.

Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose.

Arch Intern Med Mar; 5 : J Antimicrob Chemother Oct;54 4 Comparison of once-daily extended-release ciprofloxacin and conventional twice-daily ciprofloxacin for the treatment of uncomplicated urinary tract infection in women.

Clin Ther Dec;24 12 Efficacy and safety of a novel oncedaily extended-release ciprofloxacin tablet formulation for treatment of uncomplicated urinary tract infection in women.

Antimicrob Agents Chemother Oct;49 10 Single-dose enoxacin compared with 3-day treatment for urinary tract infection.

Antimicrob Agents Chemother Jun;33 6 Multicenter study of single-dose and multiple-dose fleroxacin versus ciprofloxacin in the treatment of uncomplicated urinary tract infections.

Fleroxacin in the treatment of uncomplicated urinary tract infections in women. Vienna, Austria. Jardin A. A general practitioner multicenter study: fosfomycin trometamol single dose versus pipemidic acid multiple dose.

Infection ;18 Suppl 2:S Fosfomycin trometamol in a single dose versus norfloxacin for seven days in the treatment of uncomplicated urinary infections in general practice.

Single-dose fosfomycin trometamol Monuril versus multiple-dose norfloxacin: results of a multicenter study in females with uncomplicated lower urinary tract infections.

Urol Int ;46 4 Fosfomycin trometamol in a single dose versus seven days nitrofurantoin in the treatment of acute uncomplicated urinary tract infections in women.

Pharm World Sci Dec;15 6 Analyse de 15 essais comparatifs portant sur malades. A comparison between single-dose fosfomycin trometamol Monuril and a 5-day course of trimethoprim in the treatment of uncomplicated lower urinary tract infection in women.

Int J Antimicrob Agents Apr;10 1 Comparison of single-dose fosfomycin and a 7-day course of nitrofurantoin in female patients with uncomplicated urinary tract infection.

Clin Ther Nov;21 11 Fosfomycin tromethamine in uncomplicated urinary tract infections: a clinical study.

Chemotherapy May;51 Single-dose fluoroquinolone therapy of acute uncomplicated urinary tract infection in women: results from a randomized, doubleblind, multicenter trial comparing single-dose to 3-day fluoroquinolone regimens.

Urology Mar;59 3 Gatifloxacin mg as a single shot or mg once daily for 3 days is as effective as ciprofloxacin mg twice daily for the treatment of patients with uncomplicated urinary tract infections.

Int J Antimicrob Agents Jun;23 6 A double-blind, randomised trial of the efficacy and safety of short-course, once-daily levofloxacin versus ofloxacin twice daily in uncomplicated urinary tract infection.

Infectious Diseases in Clinical Practice, Ch 9: pp. Short-course levofloxacin mg qid vs ofloxacin mg bid in uncomplicated UTI: a double-blind, randomized trial.

Lomefloxacin versus norfloxacin in the treatment of uncomplicated urinary tract infections: three-day versus seven-day treatment.

Scand J Infect Dis ;24 6 Treatment of acute uncomplicated urinary tract infections with 3 days of lomefloxacin compared with treatment with 3 days of norfloxacin.

Antimicrob Agents Chemother Mar;37 3 Br J Clin Pharmacol Aug;58 2 Nitrofurantoin modified release versus trimethoprim or co-trimoxazole in the treatment of uncomplicated urinary tract infection in general practice.

Double-blind comparison of 3-day versus 7-day treatment with norfloxacin in symptomatic urinary tract infections. Scand J Infect Dis ;20 6 Three-day versus seven-day treatment with in acute cystitis.

Curr Ther Res ; Efficacy and safety of norfloxacin mg once-daily versus norfloxacin mg twice-daily in the treatment of uncomplicated urinary tract infections in women: a double-blind, randomized clinical trial.

J Chemother Apr;10 2 Ofloxacin versus trimethoprim-sulphamethoxazole in acute cystitis. Drugs ;34 Suppl Ofloxacin versus trimethoprim-sulfamethoxazole for treatment of acute cystitis.

Antimicrob Agents Chemother Aug;33 8 Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women.

Antimicrob Agents Chemother Jul;35 7 Pefloxacin single-dose in the treatment of acute uncomplicated lower urinary tract infections in women: a meta-analysis of seven clinical trials.

Int J Antimicrob Agent, Aug;4 3 Quinolones for short-term treatment of uncomplicated urinary tract infection.

East Afr Med , ;76 10 Comparison of pivmecillinam and cephalexin in acute uncomplicated urinary tract infection.

Int J Antimicrob Agents Jan;13 3 Three days of pivmecillinam or norfloxacin for treatment of acute uncomplicated urinary infection in women.

Scand J Infect Dis ;34 7 Symptomatic vaginal candidiasis after pivmecillinam and norfloxacin treatment of acute uncomplicated lower urinary tract infection.

Int J Antimicrob Agents Oct;20 4 Clinical and bacteriological outcome of different doses and duration of pivmecillinam compared with placebo therapy of uncomplicated lower urinary tract infection in women: the LUTIW project.

Randomized, double-blind comparison of single-dose regimens of rufloxacin and pefloxacin for acute uncomplicated cystitis in women.

Antimicrob Agents Chemother Jan;39 1 Treatment of community-acquired acute uncomplicated urinary tract infection with sparfloxacin versus ofloxacin.

Antimicrob Agents Chemother Sep;42 9 Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women.

Clin Ther Jun;21 6 The treatment of acute dysuria-frequency syndrome in adult women: doubleblind, randomized comparison of three-day vs ten-day trimethoprim therapy.

Acute uncomplicated lower urinary tract infections in general practice: clinical and microbiological cure rates after three- versus five-day treatment with trimethoprim.

Eur J Gen Pract Jun;11 2 A randomised comparison of single-dose vs. Scand J Infect Dis ;16 4 Clin Infect Dis May;34 9 Failure of excessive doses of ampicillin to prevent bacterial relapse in the treatment of acute pyelonephritis.

Acta Med Scand ; 4 Short-term effectiveness of ceftriaxone single dose in the initial treatment of acute uncomplicated pyelonephritis in women.

A randomised controlled trial. Emerg Med J Jan;19 1 Once daily, extended release ciprofloxacin for complicated urinary tract infections and acute uncomplicated pyelonephritis.

J Urol Feb; 2 Pt 1 Gatifloxacin mg or mg once daily is as effective as ciprofloxacin mg twice daily for the treatment of patients with acute pyelonephritis or complicated urinary tract infections.

A doubleblind comparison, using a fixed combination of pivampicillin plus pivmecillinam. Acta Med Scand ; 5 Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days.

J Infect Dis Feb; 2 Cinoxacin prophylaxis for urinary tract infections in young women: a prospective, randomized, double-blind, placebo-controlled trial.

Advances in Therapy ;12 5 Double-blind randomized study using cinoxacin and placebo. Prophylactic efficacy of cinoxacin in recurrent urinary tract infection: biologic effects on the vaginal and fecal flora.

J Urol Jun; 6 Comparison of low-dose cinoxacin therapy and placebo in the prevention of recurrent urinary tract infections. J Fam Pract Nov;15 5 Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women.

Antimicrob Agents Chemother Jul;33 7 Low-dose norfloxacin versus placebo for long-term prophylaxis of recurrent uncomplicated urinary tract infection.

Chemioterapia Jun;6 2 Suppl Causes of the acute urethral syndrome in women. N Engl J Med Aug 21; 8 Prevention of urinary-tract infection with lowdose nitrofurantoin.

Lancet Nov 20;2 The use of small doses of cephalexin mg in the management of recurrent urinary tract infection in women. J Antimicrob Chemother ;1 3 Suppl Postcoital antimicrobial prophylaxis for recurrent urinary tract infection.

A randomized, double-blind, placebo-controlled trial. JAMA Aug; 6 A comparative trial of low dose cefaclor and macrocrystalline nitrofurantoin in the prevention of recurrent urinary tract infection.

Infection Mar-Apr;23 2 : Macrocrystalline nitrofurantoin versus norfloxacin as treatment and prophylaxis in uncomplicated recurrent urinary tract infection.

Curr Therap Res Clin Exp ; A clinical comparison between Macrodantin and trimethoprim for prophylaxis in women with recurrent urinary infections.

J Antimicrob Chemother Jul;16 1 Cinoxacin vs trimethoprim-safety and efficacy in the prophylaxis of uncomplicated urinary tract infections.

Drugs Exp Clin Res ;14 10 Post-intercourse versus daily ciprofloxacin prophylaxis for recurrent urinary tract infections in premenopausal women.

J Urol Mar; 3 Prevention of recurrent urinary infections in women: a comparative trial between nitrofurantoin and methenamine hippurate.

J Urol Jul; 1 Long-term prophylaxis of urinary infections in women: comparative trial of trimethoprim, methenamine hippurate and topical povidoneiodine.

J Urol Dec; 6 The incidence of UTI varies depending on age and sex. In the first year of life, mostly the first 3 months, UTI is more common in boys 3.

Paediatric UTI is the most common cause of fever of unknown origin in boys less than 3 years. The clinical presentation of a UTI in infants and young children can vary from fever to gastrointestinal, lower or upper urinary tract symptoms.

The objective is to rule out the unusual occurrence of obstruction, vesicoureteric reflux VUR and dysfunctional voiding, e.

Chronic pyelonephritic renal scarring develops very early in life due to the combination of a UTI, intrarenal reflux and VUR.

It sometimes arises in utero due to dysplasia. Although rare, renal scarring may lead to severe long-term complications such as hypertension and chronic renal failure.

Vesicoureteric reflux is treated with long-term prophylactic antibiotics GR: B. Surgical re-implantation or endoscopic treatment is reserved for the small number of children with breakthrough infection GR: B.

In the treatment of a UTI in children, short courses are not advised and therefore treatment is continued for days and longer GR: A.

If the child is severely ill with vomiting and dehydration, hospital admission is required and parenteral antibiotics are given initially GR: A.

It represents the most common bacterial infection in children less than 2 years of age 1 LE: 2a. The outcome of a UTI is usually benign, but in early infancy it can progress to renal scarring, especially when associated with congenital anomalies of the urinary tract.

Delayed sequelae related to renal scarring include hypertension, proteinuria, renal damage and even chronic renal failure, requiring dialysis treatment in a significant number of adults 2 LE: 2a.

The incidence is different for children under 3 months of age, when it is more common in males. The incidence of asymptomatic bacteriuria is 0.

The incidence of symptomatic bacteriuria is 0. Hospital-acquired infections show a wider pattern of aggressive organisms, such as Klebsiella, Serratia and Pseudomonas spp.

Groups A and B streptococci are relatively common in the newborn 6. There is an increasing trend towards the isolation of Staphylococcus saprophyticus in UTIs in children, although the role of this organism is still debatable 7.

Retrograde ascent is the most common mechanism of infection. Nosocomial infection and involvement as part of a systemic infection are less common 8.

Obstruction and dysfunction are among the most common causes of urinary infection. Enterobacteria derived from intestinal flora colonize the preputial sac, glandular surface and the distal urethra.

Among these organisms are strains of E. A wide variety of congenital urinary tract abnormalities can cause UTIs through obstruction, e. More mundane but significant causes of UTIs include labial adhesion and chronic constipation 7.

Dysfunctional voiding in an otherwise normal child may result in infrequent bladder emptying aided by delaying manoeuvres, e. Neuropathic bladder dysfunction spina bifida, sphincter dyssynergia, etc may lead to postvoid residual urine and secondary VUR 4.

The link between renal damage and UTIs is controversial. The mechanism in obstructive nephropathy is self-evident, but more subtle changes occur where there is VUR.

These must all work together in early childhood when the growing kidney is likely to be susceptible to parenchymal infection.

Later on in childhood, the presence of bacteriuria seems irrelevant to the progression of existing scars or the very unusual formation of new scars.

Another confounding factor is that many so-called scars are dysplastic renal tissue which developed in utero Epididymoorchitis is extremely unusual.

With scrotal pain and inflammation in a boy, testicular torsion has to be considered. A UTI in neonates may be non-specific and with no localization.

In small children, a UTI may present with gastrointestinal signs, such as vomiting and diarrhoea. In the first weeks of life, Rarely, septic shock will be the presentation.

Signs of a UTI may be vague in small children, but later on, when they are older than 2 years, frequent voiding, dysuria and suprapubic, abdominal or lumbar pain may appear with or without fever.

From the clinical point of view, severe and simple forms of UTIs should be differentiated because to some extent the severity of symptoms dictates the degree of urgency with which investigation and treatment are to be undertaken Table 3.

Table 3. The child is only slightly or not dehydrated and has a good expected level of compliance. When a low level of compliance is expected, such a child should be managed as one with a severe UTI.

The absence of fever does not exclude the presence of an infective process. Urine must be obtained under bacteriologically reliable conditions when undertaking a urine specimen culture The urine specimen may be difficult to obtain in a child less than 4 years old and different methods are advised since there is a high risk of contamination 17, In order to obtain a urine sample in the best condition in children under 2 years of age girls and uncircumcised boys without sphincteric control , it is better to use suprapubic bladder aspiration or bladder catheterization.

In older children with sphincteric control, midstream urine MSU collection is possible and reliable The presence of pyuria more than 5 leucocytes per field and bacteriuria in a fresh urine sample will reinforce the clinical diagnosis of UTI In these cases, it is better to repeat the culture or to evaluate the presence of other signs, such as pyuria, nitrites or other biochemical markers When an infection is caused by Gram-positive bacteria, the test may be negative 8, A combination of nitrite and leucocyte esterase testing improves sensitivity and specificity, but carries the risk of false-positive results The dipstick test has become useful to exclude rapidly and reliably the presence of a UTI, provided both nitrite and leucocyte esterase tests are negative.

If the tests are positive, it is better to confirm the results in combination with the clinical symptoms and other tests 17, In such cases, it is advisable to repeat the urinalysis after 24 hours to clarify the situation.

Even in febrile children with a positive urine culture, the absence of pyuria may cast doubt on the diagnosis of UTI.

Instead, asymptomatic bacteriuria with a concomitant septic focus responsible for the febrile syndrome has to be considered. Bacteriuria without pyuria is found in 0.

This figure corresponds well with the estimated rate of asymptomatic bacteriuria in childhood 20, 22 LE: 2a. Chlamydia trachomatis.

Thus, either bacteriuria or pyuria may not be considered reliable parameters to diagnose or exclude UTI. Their assessment can be influenced by other factors, such as the degree of hydration, method of specimen collection, mode of centrifugation, volume in which sediment is resuspended and subjective interpretation of results However, according to Landau et al.

For all of these reasons, in neonates and children under 6 months of age, either pyuria, bacteriuria or the nitrite test, separately, have minimal predictive value for UTI 25,26 LE: 3.

Current techniques do not fulfil all such requirements. It is subjective and therefore operator-dependent, and gives no information on renal function.

However, scars can be identified, although not as well as with technetiumm dimercaptosuccinic acid Tcm DMSA scanning 29,30 LE: 2a.

This technique has been shown to be very sensitive and excretory urography must be reserved only for when images need to be morphologically clarified 31 LE: 2a.

This technique is helpful in determining functional renal mass and ensures an accurate diagnosis of cortical scarring by showing areas of hypoactivity indicating lack of function.

A UTI interferes with the uptake of this radiotracer by the proximal renal tubular cells, and may show areas of focal defect in the renal parenchyma.

A star-shaped defect in the renal parenchyma may indicate an acute episode of pyelonephritis. A focal scarring or a smooth uniform loss of renal substance as demonstrated by Tcm DMSA has generally been regarded as being associated with VUR reflux nephropathy 35, However, Rushton et al.

Minimal parenchymal defects, when characterized by a slight area of hypoactivity, can resolve with antimicrobial therapy 39, However, defects lasting longer than 5 months are considered to be renal scarring 41 LE: 2a.

Tcm DMSA scans are considered more sensitive than excretory urography and ultrasonography in the detection of renal scars It remains questionable whether radionuclide scans could substitute for echography as a first-line diagnostic approach in children with a UTI 46, It is considered mandatory in the evaluation of UTIs in children less than 1 year of age.

Its main drawbacks are the risk of infection, the need for retrogrades filling of the bladder and the possible deleterious effect of radiation on children In recent years, tailored low-dose fluoroscopic VCU has been used for the evaluation of VUR in girls in order to minimize radiological exposure Voiding cystourethrography is mandatory in the assessment of febrile childhood UTI, even in the presence of normal ultrasonography.

It represents an attractive alternative to conventional cystography, especially when following patients with reflux, because of its lower dose of radiation.

Disadvantages are a poor image resolution and difficulty in detecting lower urinary tract abnormalities 51, Further studies are necessary to determine the role of this new imaging modality in UTI.

The major disadvantages in infants are the risks of side effects from exposure to contrast media and radiation However, the role of excretory urography is declining with the increasing technical superiority of CT 54 and MRI.

However, the indications for their use is still limited in UTI. Only a minority of children with a UTI have an underlying urological disorder, but when present such a disorder can cause considerable morbidity.

Thus, after a maximum of two UTI episodes in a girl and one episode in a boy, investigations should be undertaken Figure 3.

Figure 3. Antimicrobial treatment has to be initiated on an empirical basis, but should be adjusted according to culture results as soon as possible.

In patients with an allergy to cephalosporins, aztreonam or gentamicin may be used. When aminoglycosides are necessary, serum levels should be monitored for dose adjustment.

Chloramphenicol, sulphonamides, tetracyclines, rifampicin, amphotericin B and quinolones should be avoided. The use of ceftriaxone must also be avoided due to its undesired side effect of jaundice.

A wide variety of antimicrobials can be used in older children, with the exception of tetracyclines because of teeth staining.

Fluorinated quinolones may produce cartilage toxicity 58 , but if necessary may be used as second-line therapy in the treatment of serious infections, since musculoskeletal adverse events are of moderate intensity and transient 60, For a safety period of hours, parenteral therapy should be administered.

This provides some advantages, such as less psychological impact on the child and more comfort for the whole family. It is also less expensive, well tolerated and eventually prevents opportunistic infections However, the indication for TMP is declining in areas with increasing resistance.

UPDATE APRIL 39 In children less than 3 years of age, who have difficulty taking oral medications, parenteral treatment for days seems advisable, with similar results to those with oral treatment If there are significant abnormalities in the urinary tract e.

VUR, obstruction , appropriate urological intervention should be considered. If renal scarring is detected, the patient will need careful follow-up by a paediatrician in anticipation of sequelae such as hypertension, renal function impairment and recurrent UTI.

An overview of the treatment of febrile UTIs in children is given in Figure 3. Treatment of febrile UTIs in children.

A single parenteral dose may be used in cases of doubtful compliance and with a normal urinary tract 66 LE: 2a. If the response is poor or complications develop, the child must be admitted to hospital for parenteral treatment It may also be used after an acute episode of UTI until the diagnostic work-up is completed.

The most effective antimicrobial agents are: nitrofurantoin, TMP, cephalexin and cefaclor Jodal U. The natural history of bacteriuria in childhood.

Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up. BMJ Sep; Voiding dysfunction in children. Urol Clin North Am Aug;31 3 , ix.

Infections of the urinary tract. Pediatr Infect Dis J Feb;11 2 Nosocomial infections in pediatric intensive care units in the United States.

National Nosocomial Infections Surveillance System. Pediatrics Apr; 4 :e Staphylococcus saprophyticus urinary tract infections in children.

Eur J Pediatr Jan; 1 Urinary tract infection in children: etiology and epidemiology. Urol Clin North Am Aug;31 3 , ix-x. Effect of circumcision on incidence of urinary tract infection in preschool boys.

J Pediatr Jan; 1 Cohort study on circumcision of newborn boys and subsequent risk of urinary-tract infection.

Lancet Dec; Adherence of bacteria to human foreskins. J Urol Nov; 5 Toilet habits of children evaluated for urinary tract infection.

J Urol Aug; 2 Pt 2 The characteristics of primary vesico-ureteric reflux in male and female infants with pre-natal hydronephrosis.

Br J Urol Aug;80 2 Urinary tract infection in febrile infants younger than eight weeks of Age. Pediatrics Feb; 2 :E Diagnosis and management of pediatric urinary tract infections.

Clin Microbiol Rev Apr 2 Pediatric urinary tract infection. Urinary tract infection in children: pathophysiology, risk factors and management.

Infect Med ; Hoberman A, Wald ER. The presence of pyuria more than 5 leucocytes per field and bacteriuria in a fresh urine sample will reinforce the clinical diagnosis of UTI In these cases, it is better to repeat the culture or to evaluate the presence of other signs, such as pyuria, nitrites or other biochemical markers When an infection is caused by Gram-positive bacteria, the test may be negative 8, A combination of nitrite and leucocyte esterase testing improves sensitivity and specificity, but carries the risk of false-positive results The dipstick test has become useful to exclude rapidly and reliably the presence of a UTI, provided both nitrite and leucocyte esterase tests are negative.

If the tests are positive, it is better to confirm the results in combination with the clinical symptoms and other tests 17, In such cases, it is advisable to repeat the urinalysis after 24 hours to clarify the situation.

Even in febrile children with a positive urine culture, the absence of pyuria may cast doubt on the diagnosis of UTI. Instead, asymptomatic bacteriuria with a concomitant septic focus responsible for the febrile syndrome has to be considered.

Bacteriuria without pyuria is found in 0. This figure corresponds well with the estimated rate of asymptomatic bacteriuria in childhood 20, 22 LE: 2a.

Chlamydia trachomatis. Thus, either bacteriuria or pyuria may not be considered reliable parameters to diagnose or exclude UTI.

Their assessment can be influenced by other factors, such as the degree of hydration, method of specimen collection, mode of centrifugation, volume in which sediment is resuspended and subjective interpretation of results However, according to Landau et al.

For all of these reasons, in neonates and children under 6 months of age, either pyuria, bacteriuria or the nitrite test, separately, have minimal predictive value for UTI 25,26 LE: 3.

Current techniques do not fulfil all such requirements. It is subjective and therefore operator-dependent, and gives no information on renal function.

However, scars can be identified, although not as well as with technetiumm dimercaptosuccinic acid Tcm DMSA scanning 29,30 LE: 2a.

This technique has been shown to be very sensitive and excretory urography must be reserved only for when images need to be morphologically clarified 31 LE: 2a.

This technique is helpful in determining functional renal mass and ensures an accurate diagnosis of cortical scarring by showing areas of hypoactivity indicating lack of function.

A UTI interferes with the uptake of this radiotracer by the proximal renal tubular cells, and may show areas of focal defect in the renal parenchyma.

A star-shaped defect in the renal parenchyma may indicate an acute episode of pyelonephritis. A focal scarring or a smooth uniform loss of renal substance as demonstrated by Tcm DMSA has generally been regarded as being associated with VUR reflux nephropathy 35, However, Rushton et al.

Minimal parenchymal defects, when characterized by a slight area of hypoactivity, can resolve with antimicrobial therapy 39, However, defects lasting longer than 5 months are considered to be renal scarring 41 LE: 2a.

Tcm DMSA scans are considered more sensitive than excretory urography and ultrasonography in the detection of renal scars It remains questionable whether radionuclide scans could substitute for echography as a first-line diagnostic approach in children with a UTI 46, It is considered mandatory in the evaluation of UTIs in children less than 1 year of age.

Its main drawbacks are the risk of infection, the need for retrogrades filling of the bladder and the possible deleterious effect of radiation on children In recent years, tailored low-dose fluoroscopic VCU has been used for the evaluation of VUR in girls in order to minimize radiological exposure Voiding cystourethrography is mandatory in the assessment of febrile childhood UTI, even in the presence of normal ultrasonography.

It represents an attractive alternative to conventional cystography, especially when following patients with reflux, because of its lower dose of radiation.

Disadvantages are a poor image resolution and difficulty in detecting lower urinary tract abnormalities 51, Further studies are necessary to determine the role of this new imaging modality in UTI.

The major disadvantages in infants are the risks of side effects from exposure to contrast media and radiation However, the role of excretory urography is declining with the increasing technical superiority of CT 54 and MRI.

However, the indications for their use is still limited in UTI. Only a minority of children with a UTI have an underlying urological disorder, but when present such a disorder can cause considerable morbidity.

Thus, after a maximum of two UTI episodes in a girl and one episode in a boy, investigations should be undertaken Figure 3.

Figure 3. Antimicrobial treatment has to be initiated on an empirical basis, but should be adjusted according to culture results as soon as possible.

In patients with an allergy to cephalosporins, aztreonam or gentamicin may be used. When aminoglycosides are necessary, serum levels should be monitored for dose adjustment.

Chloramphenicol, sulphonamides, tetracyclines, rifampicin, amphotericin B and quinolones should be avoided.

The use of ceftriaxone must also be avoided due to its undesired side effect of jaundice. A wide variety of antimicrobials can be used in older children, with the exception of tetracyclines because of teeth staining.

Fluorinated quinolones may produce cartilage toxicity 58 , but if necessary may be used as second-line therapy in the treatment of serious infections, since musculoskeletal adverse events are of moderate intensity and transient 60, For a safety period of hours, parenteral therapy should be administered.

This provides some advantages, such as less psychological impact on the child and more comfort for the whole family. It is also less expensive, well tolerated and eventually prevents opportunistic infections However, the indication for TMP is declining in areas with increasing resistance.

UPDATE APRIL 39 In children less than 3 years of age, who have difficulty taking oral medications, parenteral treatment for days seems advisable, with similar results to those with oral treatment If there are significant abnormalities in the urinary tract e.

VUR, obstruction , appropriate urological intervention should be considered. If renal scarring is detected, the patient will need careful follow-up by a paediatrician in anticipation of sequelae such as hypertension, renal function impairment and recurrent UTI.

An overview of the treatment of febrile UTIs in children is given in Figure 3. Treatment of febrile UTIs in children.

A single parenteral dose may be used in cases of doubtful compliance and with a normal urinary tract 66 LE: 2a. If the response is poor or complications develop, the child must be admitted to hospital for parenteral treatment It may also be used after an acute episode of UTI until the diagnostic work-up is completed.

The most effective antimicrobial agents are: nitrofurantoin, TMP, cephalexin and cefaclor Jodal U.

The natural history of bacteriuria in childhood. Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up.

BMJ Sep; Voiding dysfunction in children. Urol Clin North Am Aug;31 3 , ix. Infections of the urinary tract. Pediatr Infect Dis J Feb;11 2 Nosocomial infections in pediatric intensive care units in the United States.

National Nosocomial Infections Surveillance System. Pediatrics Apr; 4 :e Staphylococcus saprophyticus urinary tract infections in children.

Eur J Pediatr Jan; 1 Urinary tract infection in children: etiology and epidemiology. Urol Clin North Am Aug;31 3 , ix-x.

Effect of circumcision on incidence of urinary tract infection in preschool boys. J Pediatr Jan; 1 Cohort study on circumcision of newborn boys and subsequent risk of urinary-tract infection.

Lancet Dec; Adherence of bacteria to human foreskins. J Urol Nov; 5 Toilet habits of children evaluated for urinary tract infection.

J Urol Aug; 2 Pt 2 The characteristics of primary vesico-ureteric reflux in male and female infants with pre-natal hydronephrosis.

Br J Urol Aug;80 2 Urinary tract infection in febrile infants younger than eight weeks of Age. Pediatrics Feb; 2 :E Diagnosis and management of pediatric urinary tract infections.

Clin Microbiol Rev Apr 2 Pediatric urinary tract infection. Urinary tract infection in children: pathophysiology, risk factors and management.

Infect Med ; Hoberman A, Wald ER. Urinary tract infections in young febrile children. Pediatr Infect Dis J Jan;16 1 The urine dipstick test useful to rule out infections.

A meta-analysis of the accuracy. BMC Urol Jun; Spontaneous clearance of asymptomatic bacteriuria in infants. Acta Paediatr Scand Mar;79 3 Measurement of pyuria and its relation to bacteriuria.

Am J Med Jul;75 1B The value of urinalysis in differentiating acute pyelonephritis from lower urinary tract infection in febrile infants.

Pediatr Infect Dis J Sep;13 9 Prevalence of urinary tract infection in febrile infants. J Pediatr Jul; 1 Diagnosis and management of urinary tract infections.

Curr Opin Urol Feb; Urinary N-acetylbetaglucosaminidase and betamicroglobulin in the diagnosis of urinary tract infection in febrile infants.

Pediatr Infect Dis J Apr;13 4 Interleukin 6 response to urinary tract infection in childhood. Pediatr Infect Dis J Jul;13 7 The sensitivity of renal scintigraphy and sonography in detecting nonobstructive acute pyelonephritis.

Sonographic measurement of renal enlargement in children with acute pyelonephritis and time needed for resolution: implications for renal growth assessment.

Urinary tract infection in infants and children evaluated by ultrasound. Radiology Feb; 2 Imaging in acute pyelonephritis. Curr Opin Urol Jan; Vesico-ureteric reflux in the damaged non-scarred kidney.

Pediatr Nephrol Jan;6 1 Renal radionuclide studies. Textbook of genitourinary surgery. Oxford: Blackwell Science, ; pp.

Evaluation of acute urinary tract infection in children by dimercaptosuccinic acid scintigraphy: a prospective study. J Urol Nov; 5 Pt 2 Diagnostic significance of 99mTc-dimercaptosuccinic acid DMSA scintigraphy in urinary tract infection.

Arch Dis Child Nov;67 11 Renal scarring following reflux and nonreflux pyelonephritis in children: evaluation with 99mtechnetium-dimercaptosuccinic acid scintigraphy.

J Urol May; 5 Renal papillary morphology in infants and young children. Urol Res Oct;3 3 The small scarred kidney of childhood.

A congenital or an acquired lesion. Pediatr Nephrol Oct;1 4 Renal pathology and the 99mTcDMSA image during the evolution of the early pyelonephritic scar: an experimental study.

Transient pyelonephritic changes on 99mTechnetium-dimercaptosuccinic acid scan for at least five months after infection. Acta Paediatr Aug;86 8 Evaluation of 99mtechnetium-dimercapto-succinic acid renal scans in experimental acute pyelonephritis in piglets.

Radiologic evaluation of urinary tract infection. Int Urol Nephrol ;27 1 Comparison of DMSA scintigraphy with intravenous urography for the detection of renal scarring and its correlation with vesicoureteric reflux.

Br J Urol Mar;69 3 The value of ultrasound in the child with an acute urinary tract infection. Br J Urol Aug;74 2 Does routine ultrasound have a role in the investigation of children with urinary tract infection?

Clin Radiol May;49 5 Further investigation of confirmed urinary tract infection UTI in children under five years: a systematic review.

BMC Pediatr Mar;5 1 A practical approach to evaluating urinary tract infection in children. Pediatr Nephrol Jul;5 4 Tailored low-dose fluoroscopic voiding cystourethrography for the reevaluation of vesicoureteral reflux in girls.

Paediatric urinary tract infection and the necessity of complete urological imaging. BJU Int Jul;86 1 How good is technetiumm mercaptoacetyltriglycine indirect cystography?

Eur J Nucl Med Mar;21 3 : Cystosonography and voiding cystourethrography in the diagnosis of vesicoureteral reflux.

Pediatr Nephrol Jan;18 1 Barcelona: Ed Prous, ; pp. Acute bacterial nephritis: a clinicoradiologic correlation based on computer tomography.

Am J Med Sep;93 3 Relationship among vesicoureteral reflux, Pfimbriated Escherichia coli, and acute pyelonephritis in children with febrile urinary tract infection.

J Pediatr Oct; 4 Involvement of the renal parenchyma in acute urinary tract infection: the contribution of 99mTc dimercaptosuccinic acid scan.

Eur J Pediatr Jul; 7 Pitfalls in the investigation of children with urinary tract infection. Arch Dis Child Mar;72 3 Urinary tract infection: a comparison of four methods of investigation.

Infeccion urinaria. Madrid: Ed Aula Medica, ; pp. Safety profile of quinolone antibiotics in the pediatric population.

Pediatr Infect Dis J Mar;22 12 Prescrire Int Oct;13 73 Antibiotics for acute pyelonephritis in children. DGPI ed. Futuramed: Munich, , pp.

Short versus standard duration oral antibiotic therapy for acute urinary tract infection in children. Short-course versus conventional length antimicrobial therapy for uncomplicated lower urinary tract infections in children: a meta-analysis of patients.

Efficacy of single-dose therapy of urinary tract infection in infants and children: a review. J Nalt Med Assoc Sep;86 9 Old and new concepts.

Pediatr Clin North Am Dec;42 6 : Prophylactic co-trimoxazole and trimethoprim in the management of urinary tract infection in children.

Pediatr Nephrol Jan;2 1 Vesicoureteral reflux and evidence-based management. J Pediatr Nov; 5 However, if in the adult, the kidney is normal beforehand, chronic renal damage is most unlikely.

There is no evidence that more prolonged or intensive antibiotic treatment of acute pyelonephritis will shorten the episode or prevent complications.

In diabetes mellitus, overwhelming infection can predispose to pyogenic infection with intrarenal perinephric abscess formation, emphysematous pyelonephritis, and, very rarely, a specific form of infective interstitial nephropathy.

Papillary necrosis is a common consequence of pyelonephritis in diabetics. Females are more prone to asymptomatic bacteriuria than diabetic men but in both sexes progression to clinical pyelonephritis is more likely than in normal individuals.

The risk factors for developing asymptomatic bacteriuria differ between type I and type II diabetes.

It is arguable that diabetic patients are susceptible to rapid progression of parenchymal infection. However, the clearance of asymptomatic bacteriuria should not be attempted if the intention is to prevent complications, notably acute pyelonephritis GR: A.

Typically, adult polycystic kidney disease APCKD , gross vesicoureteric reflux VUR and endstage obstructive uropathy will harbour infective foci or promote ascending infection, but not invariably so.

Clearly, severe urinary tract infection UTI with accompanying bacteraemia can hasten progression of renal failure, but there is little evidence that vigorous treatment of lesser degrees of infection or prophylaxis will slow renal functional impairment once it is established C.

Bilateral nephrectomy should be utilized as a last resort GR: B. Nephrectomy should be performed as a last resort, but even residual renal function may be of vital importance GR: B.

Obstruction may be covert and require specific diagnostic tests, e. Even so, the results of nephrectomy for a scarred or hydronephrotic kidney may be disappointing.

Immunosuppression is of secondary importance, although if this is extreme, immunosuppression will promote, at least, persistent bacteriuria, which may become symptomatic.

HIV infection is associated with acute and chronic renal disease, possibly through the mechanisms of thrombotic microangiopathy and immune mediated glomerulonephritis.

Steroids, angiotensin-converting enzyme ACE inhibitors and highly active retroviral therapy appear to have reduced progression to endstage renal disease.

There are also important scientific issues to be considered concerning the cause, special susceptibilities, effects and complications of renal parenchymal infection, particularly in the immunosuppressed patient.

This part of the guidelines can be subdivided into four sections. What are the acute effects of UTI on the kidney and do the lesions become chronic?

Does chronic renal disease progress more quickly as a result of infection and do particular renal diseases predispose to UTI?

Are immunosuppressed patients prone to UTI particularly in the context of renal transplantation? Is UTI a significant cause of graft failure?

Which problems arise in antibiotic therapy in patients with renal insufficiency and after renal transplantation? Pathologically, a similar process may occur in such fundamentally different situations as obstructive and reflux nephropathies, although the distribution and extent of the lesions may be different LE: 2a.

Renal scarring can certainly be acquired as a result of these three factors, although, in almost all cases, this usually occurs very early in life.

In this narrow age range, developmental renal dysplasia must be a major consideration in the pathogenesis of chronic pyelonephritis. Although acute infection is important in the early stages of this disease, the status of either recurrent acute urinary infection or asymptomatic bacteriuria specifically in the progression of scar formation is tenuous.

Prophylactic antibiotics will therefore offer little benefit in preserving renal tissue in reflux nephropathy in the older child and adult, even if the reflux has not already been successfully treated 6 GR: A.

However, further discussion of reflux nephropathy is beyond the scope of these guidelines. In extreme cases, pyonephrosis, perinephric abscess and widespread systemic sepsis will develop.

Obstruction has to be cleared if infection is to be eradicated 7 GR: A. A detailed discussion of obstructive nephropathy is not appropriate here, but the kidney which is permanently damaged from any cause will have less reserve to withstand the effects of reflux, obstruction and infection.

In any circumstances, the combination of obstruction and infection is a surgical emergency and both must be relieved without delay. It is sometimes difficult to exclude an element of obstruction when discussing the pathogenesis of putative infective renal damage in the alleged normal kidney.

Urinary calculi and pregnancy can cause urinary stasis and an intermittent increase in pressure in the upper tracts, which can cause subtle and persistent damage.

The presence of renal calculi and diabetes mellitus will further reduce host defences 8. They are worth reviewing as they may provide a lead in deciding how chronic changes can occur and therefore a basis for the development of guidelines on the prevention of renal damage.

Escherichia coli is the commonest of the Gram-negative organisms isolated in the majority of patients with acute pyelonephritis.

The proportion of infections caused by E. Virulent organisms cause direct cellular injury, usually after colonizing the renal pelvis.

Damage can also occur indirectly from the effects of inflammatory mediators. Metastatic infection will rarely cause renal infection, presenting as cortical abscesses and usually only in susceptible individuals see the sections below on Diabetes mellitus and Immunosuppression Bacterial infection in the urinary tract can induce fever and elevate acute phase reactants, such as C-reactive protein and erythrocyte sedimentation rate ESR.

Bacterial infection also elicits immunoglobulin A and cytokine responses 11 LE: 2b. In functional terms, there may be a loss of concentrating power which can persist long term 14,15 LE: 2b.

The fact that there is a serological immune response and bacteria become coated with antibodies to various antigenic components of the micro-organism is regarded as evidence of an immune response and therefore of exposure to micro-organisms which are potentially damaging to the renal parenchyma 16 LE: 2b.

There are many identifiable factors relating to virulence of the bacterial cell and to its ability to adhere to the mucosa as a preliminary to invasion For example, type 1 pili or fimbriae will combine with mannose receptors on the uromucoid, which is part of the protective mucopolysaccharide layer found on uroepithelial cells lining the urinary tract.

Type 2 or P fimbriae bind to glycolipids of the blood group substances which are secreted by the host urothelium.

In practical terms, E. Bacterial adhesion may be of variable benefit to the micro-organism, as its attachment may mean that it is easier for host defence mechanisms to localize and abolish it The cellular and humeral inflammatory host response is also a critical part of host defence.

Various cytokines e. IL-6, IL-8 are responsible for inducing leucocyte migration and may be intrinsically deficient in converting asymptomatic bacterial colonization to clinical infection.

Paradoxically, reduced adhesiveness can facilitate silent penetration into the renal parenchyma. In the majority of these patients, the infiltrating bacteria had reduced adhesive characteristics, perhaps facilitating their penetration into the renal parenchyma and promoting more permanent structural and functional damage 15 LE: 2b.

An earlier study by Alwall 21 described 29 women followed for years with evidence of increasing renal damage and chronic pyelonephritis upon biopsy LE: 3.

As this study would have used cruder diagnostic techniques, which might not have identified pre-existing disease, patients may have had renal damage initially.

Over such a long period, it was impossible to exclude other causes of renal impairment and interstitial nephropathy, e. This important issue is clarified by a recent more critical study of DMSA scanning during the acute phase of acute pyelonephritis.

In the study, 37 of 81 patients had one or more perfusion defects, of which the majority resolved within 3 months. In lesions that persisted, further imaging invariably showed evidence of reflux or obstructive nephropathy that must have predated the acute infective episode 22 LE: 2a.

In summary, small parenchymal scars demonstrated by modern imaging may develop as a result of acute non-obstructive pyelonephritis.

However, such patients do not develop chronic renal failure and the scar is a very different lesion from the typical scar of reflux nephropathy.

This is reflected in clinical experience. Thus, in acute pyelonephritis, IVU or DMSA scanning during an acute urinary infection can have very alarming and dramatic results, but in practical terms the observed changes will mostly resolve.

The poor correlation between the severity of the symptoms in an episode of acute pyelonephritis and the risk of permanent damage, which is very small, should discourage the clinician from prescribing excessive antibiotic treatment beyond that needed to suppress the acute inflammatory reaction GR: A.

In the future, the rare occurrence of renal damage apparently arising from acute or recurrent uncomplicated UTI may be prevented by targeting long-term treatment at selected patients.

These patients will have been identified as having an intrinsic genetic defect in the host response of cytokine release to infection.

Such a genetic defect would be even more important if a patient also had structural abnormalities causing complicated UTI.

Women with type I diabetes were particularly at risk if they had had diabetes for a long time or complications had developed, particularly peripheral neuropathy and proteinuria.

Risk factors in patients with type II diabetes were old age, proteinuria, a low body mass index and a past history of recurrent UTIs 23 LE: 2a.

Diabetes mellitus increases the risk of acute pyelonephritis from infection by Enterobacteriaceae originating in the lower urogenital tract.

Asymptomatic bacteriuria is common in female diabetics though not in males. If left untreated, it may lead to renal functional impairment The mechanism is ill-understood and, as in uncomplicated acute pyelonephritis, a direct causal link is dubious.

Other subtle factors may be present, such as an underlying diabetic nephropathy 25 and autonomic neuropathy causing voiding dysfunction.

Impaired host resistance is thought to predispose to the persistence of nephropathogenic organisms, but specific evidence is lacking for the development of renal complications.

Glycosuria inhibits phagocytosis and perhaps cellular immunity and encourages bacterial adherence. However, diabetic women with asymptomatic bacteriuria can have good glycaemic control, but still show reduced urinary cytokine and leucocyte concentration although polymorph function is normal.

Interestingly, poor glycaemic control has not been shown to increase the risk of bacteriuria It has always been recognized that diabetic patients are particularly susceptible to rapid progression of renal parenchymal infection and ensuing complications.

Until recently, there was no consensus on the questions of pre-emptive screening, treatment and prophylaxis of asymptomatic bacteriuria.

However, these issues have been addressed in a placebo-controlled double-blind randomized trial 27 LE: 1b , which concluded that treatment did not reduce complications and diabetes should not therefore be regarded as an indication for screening or treatment of asymptomatic bacteriuria.

The findings from this trial were subsequently recognized in the guidelines published by the Infectious Diseases Society of America IDSA on the diagnosis and treatment of asymptomatic bacteriuria in general Diabetic patients are also prone to an under-reported and probably unusual form of infective interstitial nephritis, which is sometimes infected by gas-forming organisms, with a high mortality emphysematous pyelonephritis This is characterized histologically by acute pyogenic infiltrate with microabscesses and the development of acute renal failure.

The origin of the organisms may be haematogenous. Even in the 48 UPDATE APRIL absence of obstruction, acute parenchymal infection may progress insidiously to form an intrarenal abscess which ruptures leading to a perinephric collection and a psoas abscess.

The presentation can occasionally be quite indolent. Papillary necrosis is common in diabetics, particularly in association with acute pyelonephritis.

It is certainly associated with permanent renal parenchymal scarring, although it is difficult to exclude obstruction by the sloughed papillae as the cause of the nephropathy.

Antibiotic prophylaxis in the treatment of asymptomatic bacteriuria is probably required GR: C.

Rarely, this can lead to endstage renal failure. However, a more subtle form of interstitial granulomatous disease can occur, which is sufficient to cause renal failure in the absence of fibrosis, calcification or obstruction 30,31 LE: 3.

Tuberculosis and leprosy can cause renal damage through the development of amyloid and also of a form of proliferative glomerulonephritis 32, LE: 2b.

For more details see EAU guidelines on genitourinary tuberculosis The antibacterial properties of normal urine, due to urea or low pH and high osmolality, may be lost Uraemic patients are also mildly immunosuppressed and the formation of protective uroepithelial mucus may be inhibited LE: 2b.

However, apart from a few exceptions, there is little evidence for a causal relationship between preexisting chronic renal disease and persisting UTI 7.

The results of removing a scarred or hydronephrotic kidney in the hope of curing infection are often disappointing.

The few exceptions include the following. It may be difficult to obtain a positive culture on standard laboratory media, but pyuria is common, particularly in the later stages of disease progression.

Acute pyelonephritis is common and may originate from pyogenic infection in the cysts 40 LE: 3. The efficacy of antibiotic treatment may depend on whether cysts are derived from proximal active secretion or distal tubules passive diffusion and on the liposolubility of the agent used.

Cephalosporins, gentamicin and ampicillin, which are standard treatments of acute pyelonephritis and require active transport, are often ineffective 41 LE; 2b.

Fluoroquinolones are generally the most effective GR: A. After transplantation, overall graft and patient survival rates do not differ between ADPK and control groups 42 LE: 2a.

However, despite close monitoring of patients, UTI and septicaemic episodes are still a significant cause of morbidity, so that bilateral nephrectomy may be the only option.

Polycystic disease is not to be confused with acquired renal cystic disease of the endstage kidney which has no predisposition to UTI.

The issue of whether urological complications including UTI affect the progression of renal failure in polycystic disease or in any other renal pathology is controversial.

However, it is doubtful whether vigorous treatment of asymptomatic bacteriuria or even mild clinical UTI will make any difference to the progression of renal disease 43 LE; 3.

It is disappointing that, as yet, there are few studies providing long-term serial data identifying renal damage and its causal relationship with infection.

In this respect, it is of some interest that a study of patients undergoing reflux prevention surgery at least 20 years before has recently been published It was concluded that even patients whose reflux prevention surgery had been successful were prone to recurrent UTI, hypertension and complications, which even occasionally included progressive renal scarring.

Clearly, the organ donor should be screened for a variety of viral and bacterial infections. Detailed discussion of this process is beyond the limits of these guidelines.

However, it must be acknowledged that the urinary tract of the cadaver donor is rarely investigated, even if the mid-stream urine MSU culture is positive.

Antibiotics are given empirically, but usually the first suspicion of occurrence of a renal tract abnormality is raised during the organ donation operation.

Under these circumstances, only the most obvious renal or ureteric abnormality will be detected.

Very occasionally, organ donation will be abandoned at this late stage. After the kidney is removed from its storage box, the effluent from the renal vein and surrounding fluid in the sterile plastic bags containing the excised kidney should ideally be cultured as micro-organisms are likely to have been introduced during the donation process.

Bladder catheters and ureteric stents promote the loss of the glycosoaminoglycan layer from the uroepithelium, as well as providing a source of micro-organism within the mucous biofilm covering the foreign body.

Infection in the native kidneys may worsen considerably as a result of maximum immunosuppression. In patients with a renal transplant the following problems are most troublesome: papillary necrosis, particularly in diabetes mellitus 46 , massive infective VUR, polycystic disease and infective calculi.

There is also concern about the increasing number of children with congenital uropathies, often associated with neuropathic bladder dysfunction and the sinister combination of intravesical obstruction, poor bladder compliance, residual urine and VUR.

A full urodynamic assessment, establishing a routine of intermittent selfcatheterization and any necessary bladder surgery must be completed well in advance of renal transplantation.

Urinary diversions and bladder augmentation and substitution have also been successfully completed in patients on dialysis treatment and after transplantation, though bacteriuria is common and may require antibiotic treatment In the first 3 months, UTI is more likely to be symptomatic with a high rate of relapse.

Later on, there is a lower rate of pyelonephritis and bacteraemia and a better response to antibiotics unless there are urological complications e.

Infarction, either of the whole kidney or of a segment due to arterial damage, can promote UTI through bacterial colonization of dead tissue.

This often occurs by commensal or fastidious pathogens. The infection may be impossible to eradicate until the kidney or at least the dead segment is removed.

There was an early suggestion that reflux into the graft could lead to pyelonephritis and parenchymal scarring.

However, these findings have not been confirmed and most surgeons do not make a special effort to perform an antireflux anastomosis.

Infection can theoretically induce graft failure by three other mechanisms, such as by the direct effect of cytokines, growth factors e.

Urinary tract infections can also reactivate cytomegalovirus infection, which can lead to acute transplant rejection.

Sometimes it can be very difficult to distinguish rejection from infection 48 LE: 2b. For many years, the polyomavirus type BK has been listed as a possible candidate for causing transplant ureteric stenosis.

The virus is susceptible to treatment with an antiviral agent cidofovir 49 LE: 2a. These may include recurrent UTI, chemical urethritis and bladder calculi of sufficient severity to warrant cystoenteric conversion.

The risk of such complications is minimized if urodynamic abnormalities, e. It is important to note that peritoneal dialysis and haemodialysis will clear certain antibiotics, which should either be avoided or given in much higher dosage.

Secondly, there are important interactions to consider between immunosuppressive agents and antibiotics. Table 4. Rifampicin and INAH not cleared by dialysis.

Give pyridoxine. Ethambutol not dialyzed. However, a short course of treatment has yet to be established and in most cases a day course of treatment will be given.

Fluoroquinolones seem to be particularly effective. There is good evidence for the beneficial effects of treating asymptomatic bacteriuria in the first 6 months after renal transplantation 51 LE: 2a.

Patients must be investigated for a surgical complication. It will also prevent Pneumocystis carinii pneumonia PCP and infection with other rare fastidious organisms.

Low-dose antibiotic prophylaxis with co-trimoxazole has been recommended for 6 months after transplantation. This will cover the high-risk period when infection is more likely to be symptomatic and associated with acute graft impairment.

A number of other drug interactions need to be considered, e. Rifampicin and eythromycin also interact with calcineurin inhibitors by increasing cytochrome p synthetase and inhibiting hepatic cyclosporin A metabolism.

In any patients with relapsing or recurrent infection, an anatomical cause, such as a urological complication in the transplant kidney or recipient bladder dysfunction, must be considered and treated vigorously.

It is wise to treat all patients even when they are asymptomatic with antifungal agents fluconazole, amphotericin B plus flucytosine.

Removal of the catheter or stents is usually necessary GR: B. Renal transplantation is possible, even when live donors and recipients have active lesions provided they are treated.

Combined medication praziquantil and oxaminoquine are recommended for 1 month. In a trial comparing infected patients with those free of schistosomiasis, there is no difference between the incidences of acute and chronic rejection.

However, UTI and urological complications occurred in the infected group and a higher cyclosporin dosage was required.

Despite this, however, it was concluded that active schistosomiasis did not preclude transplantation 53 LE: 3. For further details on schistosomiasis in genitourinary tract infections see Bichler et al.

These include HIV-induced thrombotic microangiopathy, immunemediated glomerulonephritis and nephropathy due to virus-induced cellular damage, primarily to the glomerular epithelial cell.

Combination therapy using corticosteroids, ACE inhibitors and highly active antiretroviral therapy seems to delay and prevent progression of nephropathy, although evidence from randomized trials is not available HIV infection is therefore no longer a contraindication to renal replacement therapy.

The place of immunosuppression per se in the development of UTI remains unresolved Patients with endstage renal failure are generally not particularly susceptible to the usual Gram-negative urinary pathogens, although they may acquire unusual and granulomatous infections.

Patients have evidence of reduced cellular and humoral immunity. In these patients, PCP prophylaxis of the type used in transplant patients may not reduce the rate of bacteriuria, perhaps due to the previous development of resistant organisms.

Complicated urinary tract infection in adults. In: Cattell WR, ed. Infections of the kidney and urinary tract. Frequency of development of early cortical scarring in acute primary pyelonephritis.

Kidney Int Feb;35 2 Experimental obstructive nephropathy in the pig. Renal artery changes in experimental hydronephrosis, with special reference to renal artery stenosis due to fibromuscular hyperplasia.

Br J Urol Dec;41 Suppl The pathogenesis of reflux nephropathy chronic atrophic pyelonephritis. Br J Radiol ;Suppl Obstructive uropathy.

In: Mundy AR, ed. Scientific basis of urology. Edinburgh: Churchill Livingstone , pp. Bailey RR. Vesico-ureteric reflux and reflux nephropathy.

In: Cameron S et al. Oxford textbook of clinical nephrology. Oxford: Oxford University Press,, pp. Bishop MC. Urosurgical management of urinary tract infection.

Management of pyelonephritis and upper urinary tract infections. Urol Clin North Am Nov;26 4 A prospective study of cortical scarring in acute febrile pyelonephritis in adults: clinical and bacteriological characteristics.

Clin Nephrol Mar;43 3 Urinary tract infection. Renal involvement in urinary tract infection. Kidney Int Mar;39 3 Comparison of urine and serum concentrations of interleukin-6 in women with acute pyelonephritis or asymptomatic bacteriuria.

J Infect Dis Sep; 3 Interleukin-6 and interleukin-8 in serum and urine in patients with acute pyelonephritis in relation to bacterial- virulence-associated traits and renal function.

Nephron ;67 2 Effect of bacteriuria on renal concentrating mechanisms. Ann Intern Med Apr;70 4 Bacterial attachment as a predictor of renal abnormalities in boys with urinary tract infection.

Serum antibody levels as an indication of clinically inapparent pyelonephritis. Lancet Nov; Application of laboratory research in UTI.

Occurrence of Pfimbriated Escherichia coli in urinary tract infections. Lancet Dec;2 Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses.

Primary vesicoureteric reflux as a predictor of renal damage in children hospitalized with urinary tract infection: a systematic review and metaanalysis.

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Follow-up for up to 80 months of participants in a population study and evaluation of a clinical series of 36 selected women with a history of urinary tract infection for up to 40 years.

DMSA renal scans in adults with acute pyelonephritis. Clin Nephrol Aug;46 2 Asymptomatic bacteriuria may be considered a complication in women with diabetes.

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Tubercle Mar;71 1 Association of amyloidosis with erythema nodosum leprosum reactions and recurrent neutrophil leucocytosis in leprosy.

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Basel: Karger , pp. The infectious disease problems of the diabetic renal transplant recipient. Renal function in meningomyelocele: risk factors, chronic renal failure, renal replacement therapy and transplantation.

Curr Opin Urol Nov;12 6 Renal graft rejection or urinary tract infection? The value of myeloperoxidase, C-reactive protein, and alpha2-macroglobulin in the urine.

Transplantation Aug;64 3 BK transplant nephropathy successfully treated with cidofovir. Nephrol Dial Transplant May;18 5 Urodynamic testing predicts long term urological complications following simultaneous pancreas-kidney transplantation.

Clin Transplant Feb;17 1 Posttransplant microbiological surveillance. A prospective, randomised double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: clinical efficacy, absorption of trimethoprim-sulphamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis.

Am J Med Sep;89 3 Nephrol Dial Transplant Nov;16 11 Eur Urol Jun;49 6 : Pathogenesis and treatment of HIV-associated renal diseases: lessons from clinical and animal studies, molecular pathologic correlations, and genetic investigations.

Ann Intern Med Aug; 3 Urinary tract infection in the immunocompromised host. Lessons from kidney transplantation and the AIDS epidemic.

Bacteriuria in male patients infected with human immunodeficiency virus type 1. Basel: Karger, , pp. Information has been derived from the following standard reference sources: 1.

British national formulary. Summary of product characteristics from electronic medicines compendium for individual drugs.

Datapharm Communications Ltd. Ashley C, Currie A. The renal drug handbook. Oxford: Radcliffe Medical Press, A broad range of bacteria can cause a complicated UTI.

The spectrum is much larger than in uncomplicated UTIs and bacteria are more likely to be resistant to antimicrobials, especially in a treatmentrelated complicated UTI.

Enterobacteriaceae are the predominant pathogens, with Escherichia coli being the most common pathogen.

However, non-fermenters e. Pseudomonas aeruginosa and Gram-positive cocci e. Treatment strategy depends on the severity of the illness.

Treatment encompasses three goals: management of the urological abnormality, antimicrobial therapy, and supportive care when needed.

Hospitalization is often required. To avoid the emergence of resistant strains, therapy should be guided by urine culture whenever possible.

If empirical therapy is necessary, the antibacterial spectrum of the antibiotic agent should include the most relevant pathogens GR: A. In case of failure of initial therapy, or in case of clinically severe infection, a broader-spectrum antibiotic should be chosen that is also active against Pseudomonas LE: 1b, GR: B , e.

Until predisposing factors are completely removed, true cure without recurrent infection is usually not possible.

Therefore, a urine culture should be carried out days after the completion of therapy and also weeks later GR: B.

Two criteria are mandatory to define a complicated UTI: a positive urine culture and one or more of the factors listed in Table 5.

Table 5. But neither patient age nor gender per se are part of the definition of a complicated UTI.

With regard to prognosis and clinical studies, it is advisable to stratify complicated UTIs due to urological disorders into at least two groups 4 : 1.

Patients in whom the complicating factors could be eliminated by therapy, e. Patients in whom the complicating factor could not be or is not removed satisfactorily during therapy, e.

Clinical presentation may vary from severe obstructive acute pyelonephritis with imminent urosepsis to a catheter-associated post-operative UTI, which might disappear spontaneously as soon as the catheter is removed.

These are discussed in more details in Sections 4.

Interleukin 6 response to urinary tract infection in childhood. J Urol Dec; 6 BMJ Jun; In for captive deutsch understand suprapubic bladder puncture specimen, any count of bacteria is relevant. The findings from this trial were subsequently recognized in the guidelines published by the Infectious Diseases Society of America IDSA on the diagnosis and treatment of asymptomatic bacteriuria in general

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Three-day versus seven-day treatment with in acute cystitis. Curr Ther Res ; Efficacy and safety of norfloxacin mg once-daily versus norfloxacin mg twice-daily in the treatment of uncomplicated urinary tract infections in women: a double-blind, randomized clinical trial.

J Chemother Apr;10 2 Ofloxacin versus trimethoprim-sulphamethoxazole in acute cystitis. Drugs ;34 Suppl Ofloxacin versus trimethoprim-sulfamethoxazole for treatment of acute cystitis.

Antimicrob Agents Chemother Aug;33 8 Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women.

Antimicrob Agents Chemother Jul;35 7 Pefloxacin single-dose in the treatment of acute uncomplicated lower urinary tract infections in women: a meta-analysis of seven clinical trials.

Int J Antimicrob Agent, Aug;4 3 Quinolones for short-term treatment of uncomplicated urinary tract infection. East Afr Med , ;76 10 Comparison of pivmecillinam and cephalexin in acute uncomplicated urinary tract infection.

Int J Antimicrob Agents Jan;13 3 Three days of pivmecillinam or norfloxacin for treatment of acute uncomplicated urinary infection in women.

Scand J Infect Dis ;34 7 Symptomatic vaginal candidiasis after pivmecillinam and norfloxacin treatment of acute uncomplicated lower urinary tract infection.

Int J Antimicrob Agents Oct;20 4 Clinical and bacteriological outcome of different doses and duration of pivmecillinam compared with placebo therapy of uncomplicated lower urinary tract infection in women: the LUTIW project.

Randomized, double-blind comparison of single-dose regimens of rufloxacin and pefloxacin for acute uncomplicated cystitis in women.

Antimicrob Agents Chemother Jan;39 1 Treatment of community-acquired acute uncomplicated urinary tract infection with sparfloxacin versus ofloxacin.

Antimicrob Agents Chemother Sep;42 9 Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women.

Clin Ther Jun;21 6 The treatment of acute dysuria-frequency syndrome in adult women: doubleblind, randomized comparison of three-day vs ten-day trimethoprim therapy.

Acute uncomplicated lower urinary tract infections in general practice: clinical and microbiological cure rates after three- versus five-day treatment with trimethoprim.

Eur J Gen Pract Jun;11 2 A randomised comparison of single-dose vs. Scand J Infect Dis ;16 4 Clin Infect Dis May;34 9 Failure of excessive doses of ampicillin to prevent bacterial relapse in the treatment of acute pyelonephritis.

Acta Med Scand ; 4 Short-term effectiveness of ceftriaxone single dose in the initial treatment of acute uncomplicated pyelonephritis in women.

A randomised controlled trial. Emerg Med J Jan;19 1 Once daily, extended release ciprofloxacin for complicated urinary tract infections and acute uncomplicated pyelonephritis.

J Urol Feb; 2 Pt 1 Gatifloxacin mg or mg once daily is as effective as ciprofloxacin mg twice daily for the treatment of patients with acute pyelonephritis or complicated urinary tract infections.

A doubleblind comparison, using a fixed combination of pivampicillin plus pivmecillinam. Acta Med Scand ; 5 Therapy for women hospitalized with acute pyelonephritis: a randomized trial of ampicillin versus trimethoprim-sulfamethoxazole for 14 days.

J Infect Dis Feb; 2 Cinoxacin prophylaxis for urinary tract infections in young women: a prospective, randomized, double-blind, placebo-controlled trial.

Advances in Therapy ;12 5 Double-blind randomized study using cinoxacin and placebo. Prophylactic efficacy of cinoxacin in recurrent urinary tract infection: biologic effects on the vaginal and fecal flora.

J Urol Jun; 6 Comparison of low-dose cinoxacin therapy and placebo in the prevention of recurrent urinary tract infections.

J Fam Pract Nov;15 5 Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women.

Antimicrob Agents Chemother Jul;33 7 Low-dose norfloxacin versus placebo for long-term prophylaxis of recurrent uncomplicated urinary tract infection.

Chemioterapia Jun;6 2 Suppl Causes of the acute urethral syndrome in women. N Engl J Med Aug 21; 8 Prevention of urinary-tract infection with lowdose nitrofurantoin.

Lancet Nov 20;2 The use of small doses of cephalexin mg in the management of recurrent urinary tract infection in women. J Antimicrob Chemother ;1 3 Suppl Postcoital antimicrobial prophylaxis for recurrent urinary tract infection.

A randomized, double-blind, placebo-controlled trial. JAMA Aug; 6 A comparative trial of low dose cefaclor and macrocrystalline nitrofurantoin in the prevention of recurrent urinary tract infection.

Infection Mar-Apr;23 2 : Macrocrystalline nitrofurantoin versus norfloxacin as treatment and prophylaxis in uncomplicated recurrent urinary tract infection.

Curr Therap Res Clin Exp ; A clinical comparison between Macrodantin and trimethoprim for prophylaxis in women with recurrent urinary infections.

J Antimicrob Chemother Jul;16 1 Cinoxacin vs trimethoprim-safety and efficacy in the prophylaxis of uncomplicated urinary tract infections.

Drugs Exp Clin Res ;14 10 Post-intercourse versus daily ciprofloxacin prophylaxis for recurrent urinary tract infections in premenopausal women.

J Urol Mar; 3 Prevention of recurrent urinary infections in women: a comparative trial between nitrofurantoin and methenamine hippurate.

J Urol Jul; 1 Long-term prophylaxis of urinary infections in women: comparative trial of trimethoprim, methenamine hippurate and topical povidoneiodine.

J Urol Dec; 6 The incidence of UTI varies depending on age and sex. In the first year of life, mostly the first 3 months, UTI is more common in boys 3.

Paediatric UTI is the most common cause of fever of unknown origin in boys less than 3 years.

The clinical presentation of a UTI in infants and young children can vary from fever to gastrointestinal, lower or upper urinary tract symptoms.

The objective is to rule out the unusual occurrence of obstruction, vesicoureteric reflux VUR and dysfunctional voiding, e. Chronic pyelonephritic renal scarring develops very early in life due to the combination of a UTI, intrarenal reflux and VUR.

It sometimes arises in utero due to dysplasia. Although rare, renal scarring may lead to severe long-term complications such as hypertension and chronic renal failure.

Vesicoureteric reflux is treated with long-term prophylactic antibiotics GR: B. Surgical re-implantation or endoscopic treatment is reserved for the small number of children with breakthrough infection GR: B.

In the treatment of a UTI in children, short courses are not advised and therefore treatment is continued for days and longer GR: A.

If the child is severely ill with vomiting and dehydration, hospital admission is required and parenteral antibiotics are given initially GR: A.

It represents the most common bacterial infection in children less than 2 years of age 1 LE: 2a. The outcome of a UTI is usually benign, but in early infancy it can progress to renal scarring, especially when associated with congenital anomalies of the urinary tract.

Delayed sequelae related to renal scarring include hypertension, proteinuria, renal damage and even chronic renal failure, requiring dialysis treatment in a significant number of adults 2 LE: 2a.

The incidence is different for children under 3 months of age, when it is more common in males. The incidence of asymptomatic bacteriuria is 0.

The incidence of symptomatic bacteriuria is 0. Hospital-acquired infections show a wider pattern of aggressive organisms, such as Klebsiella, Serratia and Pseudomonas spp.

Groups A and B streptococci are relatively common in the newborn 6. There is an increasing trend towards the isolation of Staphylococcus saprophyticus in UTIs in children, although the role of this organism is still debatable 7.

Retrograde ascent is the most common mechanism of infection. Nosocomial infection and involvement as part of a systemic infection are less common 8.

Obstruction and dysfunction are among the most common causes of urinary infection. Enterobacteria derived from intestinal flora colonize the preputial sac, glandular surface and the distal urethra.

Among these organisms are strains of E. A wide variety of congenital urinary tract abnormalities can cause UTIs through obstruction, e.

More mundane but significant causes of UTIs include labial adhesion and chronic constipation 7. Dysfunctional voiding in an otherwise normal child may result in infrequent bladder emptying aided by delaying manoeuvres, e.

Neuropathic bladder dysfunction spina bifida, sphincter dyssynergia, etc may lead to postvoid residual urine and secondary VUR 4.

The link between renal damage and UTIs is controversial. The mechanism in obstructive nephropathy is self-evident, but more subtle changes occur where there is VUR.

These must all work together in early childhood when the growing kidney is likely to be susceptible to parenchymal infection.

Later on in childhood, the presence of bacteriuria seems irrelevant to the progression of existing scars or the very unusual formation of new scars.

Another confounding factor is that many so-called scars are dysplastic renal tissue which developed in utero Epididymoorchitis is extremely unusual.

With scrotal pain and inflammation in a boy, testicular torsion has to be considered. A UTI in neonates may be non-specific and with no localization.

In small children, a UTI may present with gastrointestinal signs, such as vomiting and diarrhoea. In the first weeks of life, Rarely, septic shock will be the presentation.

Signs of a UTI may be vague in small children, but later on, when they are older than 2 years, frequent voiding, dysuria and suprapubic, abdominal or lumbar pain may appear with or without fever.

From the clinical point of view, severe and simple forms of UTIs should be differentiated because to some extent the severity of symptoms dictates the degree of urgency with which investigation and treatment are to be undertaken Table 3.

Table 3. The child is only slightly or not dehydrated and has a good expected level of compliance. When a low level of compliance is expected, such a child should be managed as one with a severe UTI.

The absence of fever does not exclude the presence of an infective process. Urine must be obtained under bacteriologically reliable conditions when undertaking a urine specimen culture The urine specimen may be difficult to obtain in a child less than 4 years old and different methods are advised since there is a high risk of contamination 17, In order to obtain a urine sample in the best condition in children under 2 years of age girls and uncircumcised boys without sphincteric control , it is better to use suprapubic bladder aspiration or bladder catheterization.

In older children with sphincteric control, midstream urine MSU collection is possible and reliable The presence of pyuria more than 5 leucocytes per field and bacteriuria in a fresh urine sample will reinforce the clinical diagnosis of UTI In these cases, it is better to repeat the culture or to evaluate the presence of other signs, such as pyuria, nitrites or other biochemical markers When an infection is caused by Gram-positive bacteria, the test may be negative 8, A combination of nitrite and leucocyte esterase testing improves sensitivity and specificity, but carries the risk of false-positive results The dipstick test has become useful to exclude rapidly and reliably the presence of a UTI, provided both nitrite and leucocyte esterase tests are negative.

If the tests are positive, it is better to confirm the results in combination with the clinical symptoms and other tests 17, In such cases, it is advisable to repeat the urinalysis after 24 hours to clarify the situation.

Even in febrile children with a positive urine culture, the absence of pyuria may cast doubt on the diagnosis of UTI.

Instead, asymptomatic bacteriuria with a concomitant septic focus responsible for the febrile syndrome has to be considered.

Bacteriuria without pyuria is found in 0. This figure corresponds well with the estimated rate of asymptomatic bacteriuria in childhood 20, 22 LE: 2a.

Chlamydia trachomatis. Thus, either bacteriuria or pyuria may not be considered reliable parameters to diagnose or exclude UTI.

Their assessment can be influenced by other factors, such as the degree of hydration, method of specimen collection, mode of centrifugation, volume in which sediment is resuspended and subjective interpretation of results However, according to Landau et al.

For all of these reasons, in neonates and children under 6 months of age, either pyuria, bacteriuria or the nitrite test, separately, have minimal predictive value for UTI 25,26 LE: 3.

Current techniques do not fulfil all such requirements. It is subjective and therefore operator-dependent, and gives no information on renal function.

However, scars can be identified, although not as well as with technetiumm dimercaptosuccinic acid Tcm DMSA scanning 29,30 LE: 2a. This technique has been shown to be very sensitive and excretory urography must be reserved only for when images need to be morphologically clarified 31 LE: 2a.

This technique is helpful in determining functional renal mass and ensures an accurate diagnosis of cortical scarring by showing areas of hypoactivity indicating lack of function.

A UTI interferes with the uptake of this radiotracer by the proximal renal tubular cells, and may show areas of focal defect in the renal parenchyma.

A star-shaped defect in the renal parenchyma may indicate an acute episode of pyelonephritis. A focal scarring or a smooth uniform loss of renal substance as demonstrated by Tcm DMSA has generally been regarded as being associated with VUR reflux nephropathy 35, However, Rushton et al.

Minimal parenchymal defects, when characterized by a slight area of hypoactivity, can resolve with antimicrobial therapy 39, However, defects lasting longer than 5 months are considered to be renal scarring 41 LE: 2a.

Tcm DMSA scans are considered more sensitive than excretory urography and ultrasonography in the detection of renal scars It remains questionable whether radionuclide scans could substitute for echography as a first-line diagnostic approach in children with a UTI 46, It is considered mandatory in the evaluation of UTIs in children less than 1 year of age.

Its main drawbacks are the risk of infection, the need for retrogrades filling of the bladder and the possible deleterious effect of radiation on children In recent years, tailored low-dose fluoroscopic VCU has been used for the evaluation of VUR in girls in order to minimize radiological exposure Voiding cystourethrography is mandatory in the assessment of febrile childhood UTI, even in the presence of normal ultrasonography.

It represents an attractive alternative to conventional cystography, especially when following patients with reflux, because of its lower dose of radiation.

Disadvantages are a poor image resolution and difficulty in detecting lower urinary tract abnormalities 51, Further studies are necessary to determine the role of this new imaging modality in UTI.

The major disadvantages in infants are the risks of side effects from exposure to contrast media and radiation However, the role of excretory urography is declining with the increasing technical superiority of CT 54 and MRI.

However, the indications for their use is still limited in UTI. Only a minority of children with a UTI have an underlying urological disorder, but when present such a disorder can cause considerable morbidity.

Thus, after a maximum of two UTI episodes in a girl and one episode in a boy, investigations should be undertaken Figure 3. Figure 3. Antimicrobial treatment has to be initiated on an empirical basis, but should be adjusted according to culture results as soon as possible.

In patients with an allergy to cephalosporins, aztreonam or gentamicin may be used. When aminoglycosides are necessary, serum levels should be monitored for dose adjustment.

Chloramphenicol, sulphonamides, tetracyclines, rifampicin, amphotericin B and quinolones should be avoided.

The use of ceftriaxone must also be avoided due to its undesired side effect of jaundice. A wide variety of antimicrobials can be used in older children, with the exception of tetracyclines because of teeth staining.

Fluorinated quinolones may produce cartilage toxicity 58 , but if necessary may be used as second-line therapy in the treatment of serious infections, since musculoskeletal adverse events are of moderate intensity and transient 60, For a safety period of hours, parenteral therapy should be administered.

This provides some advantages, such as less psychological impact on the child and more comfort for the whole family.

It is also less expensive, well tolerated and eventually prevents opportunistic infections However, the indication for TMP is declining in areas with increasing resistance.

UPDATE APRIL 39 In children less than 3 years of age, who have difficulty taking oral medications, parenteral treatment for days seems advisable, with similar results to those with oral treatment If there are significant abnormalities in the urinary tract e.

VUR, obstruction , appropriate urological intervention should be considered. If renal scarring is detected, the patient will need careful follow-up by a paediatrician in anticipation of sequelae such as hypertension, renal function impairment and recurrent UTI.

An overview of the treatment of febrile UTIs in children is given in Figure 3. Treatment of febrile UTIs in children. A single parenteral dose may be used in cases of doubtful compliance and with a normal urinary tract 66 LE: 2a.

If the response is poor or complications develop, the child must be admitted to hospital for parenteral treatment It may also be used after an acute episode of UTI until the diagnostic work-up is completed.

The most effective antimicrobial agents are: nitrofurantoin, TMP, cephalexin and cefaclor Jodal U. The natural history of bacteriuria in childhood.

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Lancet Dec; Adherence of bacteria to human foreskins. J Urol Nov; 5 Toilet habits of children evaluated for urinary tract infection.

J Urol Aug; 2 Pt 2 The characteristics of primary vesico-ureteric reflux in male and female infants with pre-natal hydronephrosis.

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A meta-analysis of the accuracy. BMC Urol Jun; Spontaneous clearance of asymptomatic bacteriuria in infants. Acta Paediatr Scand Mar;79 3 Measurement of pyuria and its relation to bacteriuria.

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Sonographic measurement of renal enlargement in children with acute pyelonephritis and time needed for resolution: implications for renal growth assessment.

Urinary tract infection in infants and children evaluated by ultrasound. Radiology Feb; 2 Imaging in acute pyelonephritis. Curr Opin Urol Jan; Vesico-ureteric reflux in the damaged non-scarred kidney.

Pediatr Nephrol Jan;6 1 Renal radionuclide studies. Textbook of genitourinary surgery. Oxford: Blackwell Science, ; pp. Evaluation of acute urinary tract infection in children by dimercaptosuccinic acid scintigraphy: a prospective study.

J Urol Nov; 5 Pt 2 Diagnostic significance of 99mTc-dimercaptosuccinic acid DMSA scintigraphy in urinary tract infection.

Arch Dis Child Nov;67 11 Renal scarring following reflux and nonreflux pyelonephritis in children: evaluation with 99mtechnetium-dimercaptosuccinic acid scintigraphy.

J Urol May; 5 Renal papillary morphology in infants and young children. Urol Res Oct;3 3 The small scarred kidney of childhood.

A congenital or an acquired lesion. Pediatr Nephrol Oct;1 4 Renal pathology and the 99mTcDMSA image during the evolution of the early pyelonephritic scar: an experimental study.

Transient pyelonephritic changes on 99mTechnetium-dimercaptosuccinic acid scan for at least five months after infection.

Acta Paediatr Aug;86 8 Evaluation of 99mtechnetium-dimercapto-succinic acid renal scans in experimental acute pyelonephritis in piglets.

Radiologic evaluation of urinary tract infection. Int Urol Nephrol ;27 1 Comparison of DMSA scintigraphy with intravenous urography for the detection of renal scarring and its correlation with vesicoureteric reflux.

Br J Urol Mar;69 3 The value of ultrasound in the child with an acute urinary tract infection. Br J Urol Aug;74 2 Does routine ultrasound have a role in the investigation of children with urinary tract infection?

Clin Radiol May;49 5 Further investigation of confirmed urinary tract infection UTI in children under five years: a systematic review.

BMC Pediatr Mar;5 1 A practical approach to evaluating urinary tract infection in children.

Pediatr Nephrol Jul;5 4 Tailored low-dose fluoroscopic voiding cystourethrography for the reevaluation of vesicoureteral reflux in girls.

Paediatric urinary tract infection and the necessity of complete urological imaging. BJU Int Jul;86 1 How good is technetiumm mercaptoacetyltriglycine indirect cystography?

Eur J Nucl Med Mar;21 3 : Cystosonography and voiding cystourethrography in the diagnosis of vesicoureteral reflux.

Pediatr Nephrol Jan;18 1 Barcelona: Ed Prous, ; pp. Acute bacterial nephritis: a clinicoradiologic correlation based on computer tomography.

Am J Med Sep;93 3 Relationship among vesicoureteral reflux, Pfimbriated Escherichia coli, and acute pyelonephritis in children with febrile urinary tract infection.

J Pediatr Oct; 4 Involvement of the renal parenchyma in acute urinary tract infection: the contribution of 99mTc dimercaptosuccinic acid scan.

Eur J Pediatr Jul; 7 Pitfalls in the investigation of children with urinary tract infection.

Arch Dis Child Mar;72 3 Urinary tract infection: a comparison of four methods of investigation. Infeccion urinaria.

Madrid: Ed Aula Medica, ; pp. Safety profile of quinolone antibiotics in the pediatric population. Pediatr Infect Dis J Mar;22 12 Prescrire Int Oct;13 73 Antibiotics for acute pyelonephritis in children.

DGPI ed. Futuramed: Munich, , pp. Short versus standard duration oral antibiotic therapy for acute urinary tract infection in children.

Short-course versus conventional length antimicrobial therapy for uncomplicated lower urinary tract infections in children: a meta-analysis of patients.

Efficacy of single-dose therapy of urinary tract infection in infants and children: a review.

J Nalt Med Assoc Sep;86 9 Old and new concepts. Pediatr Clin North Am Dec;42 6 : Prophylactic co-trimoxazole and trimethoprim in the management of urinary tract infection in children.

Pediatr Nephrol Jan;2 1 Vesicoureteral reflux and evidence-based management. J Pediatr Nov; 5 However, if in the adult, the kidney is normal beforehand, chronic renal damage is most unlikely.

There is no evidence that more prolonged or intensive antibiotic treatment of acute pyelonephritis will shorten the episode or prevent complications.

In diabetes mellitus, overwhelming infection can predispose to pyogenic infection with intrarenal perinephric abscess formation, emphysematous pyelonephritis, and, very rarely, a specific form of infective interstitial nephropathy.

Papillary necrosis is a common consequence of pyelonephritis in diabetics. Females are more prone to asymptomatic bacteriuria than diabetic men but in both sexes progression to clinical pyelonephritis is more likely than in normal individuals.

The risk factors for developing asymptomatic bacteriuria differ between type I and type II diabetes. It is arguable that diabetic patients are susceptible to rapid progression of parenchymal infection.

However, the clearance of asymptomatic bacteriuria should not be attempted if the intention is to prevent complications, notably acute pyelonephritis GR: A.

Typically, adult polycystic kidney disease APCKD , gross vesicoureteric reflux VUR and endstage obstructive uropathy will harbour infective foci or promote ascending infection, but not invariably so.

Clearly, severe urinary tract infection UTI with accompanying bacteraemia can hasten progression of renal failure, but there is little evidence that vigorous treatment of lesser degrees of infection or prophylaxis will slow renal functional impairment once it is established C.

Bilateral nephrectomy should be utilized as a last resort GR: B. Nephrectomy should be performed as a last resort, but even residual renal function may be of vital importance GR: B.

Obstruction may be covert and require specific diagnostic tests, e. Even so, the results of nephrectomy for a scarred or hydronephrotic kidney may be disappointing.

Immunosuppression is of secondary importance, although if this is extreme, immunosuppression will promote, at least, persistent bacteriuria, which may become symptomatic.

HIV infection is associated with acute and chronic renal disease, possibly through the mechanisms of thrombotic microangiopathy and immune mediated glomerulonephritis.

Steroids, angiotensin-converting enzyme ACE inhibitors and highly active retroviral therapy appear to have reduced progression to endstage renal disease.

There are also important scientific issues to be considered concerning the cause, special susceptibilities, effects and complications of renal parenchymal infection, particularly in the immunosuppressed patient.

This part of the guidelines can be subdivided into four sections. What are the acute effects of UTI on the kidney and do the lesions become chronic?

Does chronic renal disease progress more quickly as a result of infection and do particular renal diseases predispose to UTI?

Are immunosuppressed patients prone to UTI particularly in the context of renal transplantation?

Is UTI a significant cause of graft failure? Which problems arise in antibiotic therapy in patients with renal insufficiency and after renal transplantation?

Pathologically, a similar process may occur in such fundamentally different situations as obstructive and reflux nephropathies, although the distribution and extent of the lesions may be different LE: 2a.

Renal scarring can certainly be acquired as a result of these three factors, although, in almost all cases, this usually occurs very early in life.

In this narrow age range, developmental renal dysplasia must be a major consideration in the pathogenesis of chronic pyelonephritis.

Although acute infection is important in the early stages of this disease, the status of either recurrent acute urinary infection or asymptomatic bacteriuria specifically in the progression of scar formation is tenuous.

Prophylactic antibiotics will therefore offer little benefit in preserving renal tissue in reflux nephropathy in the older child and adult, even if the reflux has not already been successfully treated 6 GR: A.

However, further discussion of reflux nephropathy is beyond the scope of these guidelines. In extreme cases, pyonephrosis, perinephric abscess and widespread systemic sepsis will develop.

Obstruction has to be cleared if infection is to be eradicated 7 GR: A. A detailed discussion of obstructive nephropathy is not appropriate here, but the kidney which is permanently damaged from any cause will have less reserve to withstand the effects of reflux, obstruction and infection.

In any circumstances, the combination of obstruction and infection is a surgical emergency and both must be relieved without delay.

It is sometimes difficult to exclude an element of obstruction when discussing the pathogenesis of putative infective renal damage in the alleged normal kidney.

Urinary calculi and pregnancy can cause urinary stasis and an intermittent increase in pressure in the upper tracts, which can cause subtle and persistent damage.

The presence of renal calculi and diabetes mellitus will further reduce host defences 8. They are worth reviewing as they may provide a lead in deciding how chronic changes can occur and therefore a basis for the development of guidelines on the prevention of renal damage.

Escherichia coli is the commonest of the Gram-negative organisms isolated in the majority of patients with acute pyelonephritis. The proportion of infections caused by E.

Virulent organisms cause direct cellular injury, usually after colonizing the renal pelvis. Damage can also occur indirectly from the effects of inflammatory mediators.

Metastatic infection will rarely cause renal infection, presenting as cortical abscesses and usually only in susceptible individuals see the sections below on Diabetes mellitus and Immunosuppression Bacterial infection in the urinary tract can induce fever and elevate acute phase reactants, such as C-reactive protein and erythrocyte sedimentation rate ESR.

Bacterial infection also elicits immunoglobulin A and cytokine responses 11 LE: 2b. In functional terms, there may be a loss of concentrating power which can persist long term 14,15 LE: 2b.

The fact that there is a serological immune response and bacteria become coated with antibodies to various antigenic components of the micro-organism is regarded as evidence of an immune response and therefore of exposure to micro-organisms which are potentially damaging to the renal parenchyma 16 LE: 2b.

There are many identifiable factors relating to virulence of the bacterial cell and to its ability to adhere to the mucosa as a preliminary to invasion For example, type 1 pili or fimbriae will combine with mannose receptors on the uromucoid, which is part of the protective mucopolysaccharide layer found on uroepithelial cells lining the urinary tract.

Type 2 or P fimbriae bind to glycolipids of the blood group substances which are secreted by the host urothelium. In practical terms, E.

Bacterial adhesion may be of variable benefit to the micro-organism, as its attachment may mean that it is easier for host defence mechanisms to localize and abolish it The cellular and humeral inflammatory host response is also a critical part of host defence.

Various cytokines e. IL-6, IL-8 are responsible for inducing leucocyte migration and may be intrinsically deficient in converting asymptomatic bacterial colonization to clinical infection.

Paradoxically, reduced adhesiveness can facilitate silent penetration into the renal parenchyma. In the majority of these patients, the infiltrating bacteria had reduced adhesive characteristics, perhaps facilitating their penetration into the renal parenchyma and promoting more permanent structural and functional damage 15 LE: 2b.

An earlier study by Alwall 21 described 29 women followed for years with evidence of increasing renal damage and chronic pyelonephritis upon biopsy LE: 3.

As this study would have used cruder diagnostic techniques, which might not have identified pre-existing disease, patients may have had renal damage initially.

Over such a long period, it was impossible to exclude other causes of renal impairment and interstitial nephropathy, e. This important issue is clarified by a recent more critical study of DMSA scanning during the acute phase of acute pyelonephritis.

In the study, 37 of 81 patients had one or more perfusion defects, of which the majority resolved within 3 months.

In lesions that persisted, further imaging invariably showed evidence of reflux or obstructive nephropathy that must have predated the acute infective episode 22 LE: 2a.

In summary, small parenchymal scars demonstrated by modern imaging may develop as a result of acute non-obstructive pyelonephritis.

However, such patients do not develop chronic renal failure and the scar is a very different lesion from the typical scar of reflux nephropathy.

This is reflected in clinical experience. Thus, in acute pyelonephritis, IVU or DMSA scanning during an acute urinary infection can have very alarming and dramatic results, but in practical terms the observed changes will mostly resolve.

The poor correlation between the severity of the symptoms in an episode of acute pyelonephritis and the risk of permanent damage, which is very small, should discourage the clinician from prescribing excessive antibiotic treatment beyond that needed to suppress the acute inflammatory reaction GR: A.

In the future, the rare occurrence of renal damage apparently arising from acute or recurrent uncomplicated UTI may be prevented by targeting long-term treatment at selected patients.

These patients will have been identified as having an intrinsic genetic defect in the host response of cytokine release to infection. Such a genetic defect would be even more important if a patient also had structural abnormalities causing complicated UTI.

Women with type I diabetes were particularly at risk if they had had diabetes for a long time or complications had developed, particularly peripheral neuropathy and proteinuria.

Risk factors in patients with type II diabetes were old age, proteinuria, a low body mass index and a past history of recurrent UTIs 23 LE: 2a.

Diabetes mellitus increases the risk of acute pyelonephritis from infection by Enterobacteriaceae originating in the lower urogenital tract.

Asymptomatic bacteriuria is common in female diabetics though not in males. If left untreated, it may lead to renal functional impairment The mechanism is ill-understood and, as in uncomplicated acute pyelonephritis, a direct causal link is dubious.

Other subtle factors may be present, such as an underlying diabetic nephropathy 25 and autonomic neuropathy causing voiding dysfunction. Impaired host resistance is thought to predispose to the persistence of nephropathogenic organisms, but specific evidence is lacking for the development of renal complications.

Glycosuria inhibits phagocytosis and perhaps cellular immunity and encourages bacterial adherence. However, diabetic women with asymptomatic bacteriuria can have good glycaemic control, but still show reduced urinary cytokine and leucocyte concentration although polymorph function is normal.

Interestingly, poor glycaemic control has not been shown to increase the risk of bacteriuria It has always been recognized that diabetic patients are particularly susceptible to rapid progression of renal parenchymal infection and ensuing complications.

Until recently, there was no consensus on the questions of pre-emptive screening, treatment and prophylaxis of asymptomatic bacteriuria. However, these issues have been addressed in a placebo-controlled double-blind randomized trial 27 LE: 1b , which concluded that treatment did not reduce complications and diabetes should not therefore be regarded as an indication for screening or treatment of asymptomatic bacteriuria.

The findings from this trial were subsequently recognized in the guidelines published by the Infectious Diseases Society of America IDSA on the diagnosis and treatment of asymptomatic bacteriuria in general Diabetic patients are also prone to an under-reported and probably unusual form of infective interstitial nephritis, which is sometimes infected by gas-forming organisms, with a high mortality emphysematous pyelonephritis This is characterized histologically by acute pyogenic infiltrate with microabscesses and the development of acute renal failure.

The origin of the organisms may be haematogenous. Even in the 48 UPDATE APRIL absence of obstruction, acute parenchymal infection may progress insidiously to form an intrarenal abscess which ruptures leading to a perinephric collection and a psoas abscess.

The presentation can occasionally be quite indolent. Papillary necrosis is common in diabetics, particularly in association with acute pyelonephritis.

It is certainly associated with permanent renal parenchymal scarring, although it is difficult to exclude obstruction by the sloughed papillae as the cause of the nephropathy.

Antibiotic prophylaxis in the treatment of asymptomatic bacteriuria is probably required GR: C.

Rarely, this can lead to endstage renal failure. However, a more subtle form of interstitial granulomatous disease can occur, which is sufficient to cause renal failure in the absence of fibrosis, calcification or obstruction 30,31 LE: 3.

Tuberculosis and leprosy can cause renal damage through the development of amyloid and also of a form of proliferative glomerulonephritis 32, LE: 2b.

For more details see EAU guidelines on genitourinary tuberculosis The antibacterial properties of normal urine, due to urea or low pH and high osmolality, may be lost Uraemic patients are also mildly immunosuppressed and the formation of protective uroepithelial mucus may be inhibited LE: 2b.

However, apart from a few exceptions, there is little evidence for a causal relationship between preexisting chronic renal disease and persisting UTI 7.

The results of removing a scarred or hydronephrotic kidney in the hope of curing infection are often disappointing.

The few exceptions include the following. It may be difficult to obtain a positive culture on standard laboratory media, but pyuria is common, particularly in the later stages of disease progression.

Acute pyelonephritis is common and may originate from pyogenic infection in the cysts 40 LE: 3.

The efficacy of antibiotic treatment may depend on whether cysts are derived from proximal active secretion or distal tubules passive diffusion and on the liposolubility of the agent used.

Cephalosporins, gentamicin and ampicillin, which are standard treatments of acute pyelonephritis and require active transport, are often ineffective 41 LE; 2b.

Fluoroquinolones are generally the most effective GR: A. After transplantation, overall graft and patient survival rates do not differ between ADPK and control groups 42 LE: 2a.

However, despite close monitoring of patients, UTI and septicaemic episodes are still a significant cause of morbidity, so that bilateral nephrectomy may be the only option.

Polycystic disease is not to be confused with acquired renal cystic disease of the endstage kidney which has no predisposition to UTI.

The issue of whether urological complications including UTI affect the progression of renal failure in polycystic disease or in any other renal pathology is controversial.

However, it is doubtful whether vigorous treatment of asymptomatic bacteriuria or even mild clinical UTI will make any difference to the progression of renal disease 43 LE; 3.

It is disappointing that, as yet, there are few studies providing long-term serial data identifying renal damage and its causal relationship with infection.

In this respect, it is of some interest that a study of patients undergoing reflux prevention surgery at least 20 years before has recently been published It was concluded that even patients whose reflux prevention surgery had been successful were prone to recurrent UTI, hypertension and complications, which even occasionally included progressive renal scarring.

Clearly, the organ donor should be screened for a variety of viral and bacterial infections. Detailed discussion of this process is beyond the limits of these guidelines.

However, it must be acknowledged that the urinary tract of the cadaver donor is rarely investigated, even if the mid-stream urine MSU culture is positive.

Antibiotics are given empirically, but usually the first suspicion of occurrence of a renal tract abnormality is raised during the organ donation operation.

Under these circumstances, only the most obvious renal or ureteric abnormality will be detected. Very occasionally, organ donation will be abandoned at this late stage.

After the kidney is removed from its storage box, the effluent from the renal vein and surrounding fluid in the sterile plastic bags containing the excised kidney should ideally be cultured as micro-organisms are likely to have been introduced during the donation process.

Bladder catheters and ureteric stents promote the loss of the glycosoaminoglycan layer from the uroepithelium, as well as providing a source of micro-organism within the mucous biofilm covering the foreign body.

Infection in the native kidneys may worsen considerably as a result of maximum immunosuppression. In patients with a renal transplant the following problems are most troublesome: papillary necrosis, particularly in diabetes mellitus 46 , massive infective VUR, polycystic disease and infective calculi.

There is also concern about the increasing number of children with congenital uropathies, often associated with neuropathic bladder dysfunction and the sinister combination of intravesical obstruction, poor bladder compliance, residual urine and VUR.

A full urodynamic assessment, establishing a routine of intermittent selfcatheterization and any necessary bladder surgery must be completed well in advance of renal transplantation.

Urinary diversions and bladder augmentation and substitution have also been successfully completed in patients on dialysis treatment and after transplantation, though bacteriuria is common and may require antibiotic treatment In the first 3 months, UTI is more likely to be symptomatic with a high rate of relapse.

Later on, there is a lower rate of pyelonephritis and bacteraemia and a better response to antibiotics unless there are urological complications e.

Infarction, either of the whole kidney or of a segment due to arterial damage, can promote UTI through bacterial colonization of dead tissue.

This often occurs by commensal or fastidious pathogens. The infection may be impossible to eradicate until the kidney or at least the dead segment is removed.

There was an early suggestion that reflux into the graft could lead to pyelonephritis and parenchymal scarring.

However, these findings have not been confirmed and most surgeons do not make a special effort to perform an antireflux anastomosis.

Infection can theoretically induce graft failure by three other mechanisms, such as by the direct effect of cytokines, growth factors e.

Urinary tract infections can also reactivate cytomegalovirus infection, which can lead to acute transplant rejection. Sometimes it can be very difficult to distinguish rejection from infection 48 LE: 2b.

For many years, the polyomavirus type BK has been listed as a possible candidate for causing transplant ureteric stenosis.

The virus is susceptible to treatment with an antiviral agent cidofovir 49 LE: 2a. These may include recurrent UTI, chemical urethritis and bladder calculi of sufficient severity to warrant cystoenteric conversion.

The risk of such complications is minimized if urodynamic abnormalities, e. It is important to note that peritoneal dialysis and haemodialysis will clear certain antibiotics, which should either be avoided or given in much higher dosage.

Secondly, there are important interactions to consider between immunosuppressive agents and antibiotics. Table 4. Rifampicin and INAH not cleared by dialysis.

Give pyridoxine. Ethambutol not dialyzed. However, a short course of treatment has yet to be established and in most cases a day course of treatment will be given.

Fluoroquinolones seem to be particularly effective. There is good evidence for the beneficial effects of treating asymptomatic bacteriuria in the first 6 months after renal transplantation 51 LE: 2a.

Patients must be investigated for a surgical complication. It will also prevent Pneumocystis carinii pneumonia PCP and infection with other rare fastidious organisms.

Low-dose antibiotic prophylaxis with co-trimoxazole has been recommended for 6 months after transplantation.

This will cover the high-risk period when infection is more likely to be symptomatic and associated with acute graft impairment.

A number of other drug interactions need to be considered, e. Rifampicin and eythromycin also interact with calcineurin inhibitors by increasing cytochrome p synthetase and inhibiting hepatic cyclosporin A metabolism.

In any patients with relapsing or recurrent infection, an anatomical cause, such as a urological complication in the transplant kidney or recipient bladder dysfunction, must be considered and treated vigorously.

It is wise to treat all patients even when they are asymptomatic with antifungal agents fluconazole, amphotericin B plus flucytosine.

Removal of the catheter or stents is usually necessary GR: B. Renal transplantation is possible, even when live donors and recipients have active lesions provided they are treated.

Combined medication praziquantil and oxaminoquine are recommended for 1 month. In a trial comparing infected patients with those free of schistosomiasis, there is no difference between the incidences of acute and chronic rejection.

However, UTI and urological complications occurred in the infected group and a higher cyclosporin dosage was required.

Despite this, however, it was concluded that active schistosomiasis did not preclude transplantation 53 LE: 3. For further details on schistosomiasis in genitourinary tract infections see Bichler et al.

These include HIV-induced thrombotic microangiopathy, immunemediated glomerulonephritis and nephropathy due to virus-induced cellular damage, primarily to the glomerular epithelial cell.

Combination therapy using corticosteroids, ACE inhibitors and highly active antiretroviral therapy seems to delay and prevent progression of nephropathy, although evidence from randomized trials is not available HIV infection is therefore no longer a contraindication to renal replacement therapy.

The place of immunosuppression per se in the development of UTI remains unresolved Patients with endstage renal failure are generally not particularly susceptible to the usual Gram-negative urinary pathogens, although they may acquire unusual and granulomatous infections.

Patients have evidence of reduced cellular and humoral immunity. In these patients, PCP prophylaxis of the type used in transplant patients may not reduce the rate of bacteriuria, perhaps due to the previous development of resistant organisms.

Complicated urinary tract infection in adults. In: Cattell WR, ed. Infections of the kidney and urinary tract. Frequency of development of early cortical scarring in acute primary pyelonephritis.

Kidney Int Feb;35 2 Experimental obstructive nephropathy in the pig. Renal artery changes in experimental hydronephrosis, with special reference to renal artery stenosis due to fibromuscular hyperplasia.

Clin Microbiol Infect Sep;6 9 Def 1. DEF 2. Clin Microbiol Infect Oct;6 10 Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically.

Wayne, PA. The Netherlands, European Association of Urology. Evaluation of new anti-infective drugs for the treatment of urinary tract infection.

General guidelines for the evaluation of new anti-infective drugs for the treatment of UTI. Naber KG. Experience with the new guidelines on evaluation of new anti-infective drugs for the treatment of urinary tract infections.

Int J Antimicrob Agents May;11 ; discussion Guidelines on urinary and male genital tract infections. In: EAU Guidelines. ISBN EAU guidelines for the management of urinary and male genital tract infections.

Eur Urol Nov;40 5 Eur Urol Jul;44 1 EAU guidelines for the management of genitourinary tuberculosis. Eur Urol Sep;48 3 EAU guidelines for the management of urogenital schistosomiasis.

Eur Urol Jun;49 6 Uncomplicated urinary tract infections in adults This chapter is a summary of the ICUD initiative on urogenital infections, sections 5, 6 and 7 on uncomplicated UTIs 1.

These UTIs are seen mostly in women without relevant structural and functional abnormalities within the urinary tract, kidney diseases, and comorbidity that can lead to more serious outcomes and therefore require additional care 2.

Occasionally, other Enterobacteriaceae, such as Proteus mirabilis and Klebsiella spp. Diagnosis 2.

Women who present with atypical symptoms of either acute uncomplicated cystitis or acute uncomplicated pyelonephritis, as well as those who fail to respond to appropriate antimicrobial therapy should be considered for additional diagnostic studies LE:4, GR: B.

According to these principles and the available susceptibility patterns in Europe, fosfomycin trometamol 3 g single dose, pivmecillinam mg for 3 days, and nitrofurantoin macrocrystal mg bid for 5 days, are considered as drugs of first choice in many countries, when available LE: 1a, GR: A.

Alternative antibiotics are ciprofloxacin mg bid, ciprofloxacin extended release mg qd, levofloxacin mg qd, norfloxacin mg bid, and ofloxacin mg bid, each as a 3-day course 16 LE: 1b, GR: B.

However, adverse effects have to be considered Table 2. Table 2. In women whose symptoms do not resolve by the end of treatment, and in those whose symptoms resolve but recur within 2 weeks, urine culture and antimicrobial susceptibility tests should be performed LE: 4, GR: B.

For therapy in this situation, one should assume that the infecting organism is not susceptible to the agent originally used.

Additional investigations, such as an unenhanced helical computed tomography CT , excretory urography, or dimercaptosuccinic acid DMSA scanning, should be considered if the patients remain febrile after 72 h of treatment LE: 4, GR: C.

However, S. A fluoroquinolone for days can be recommended as first-line therapy if the resistance rate of E. If the fluoroquinolone dose is increased, the treatment can probably be reduced to 5 days 22,23 LE: 1b, GR: B.

However, increasing numbers of fluoroquinolone-resistant E. A third-generation oral cephalosporin, such as cefpodoxime proxetil or ceftibuten, could be an alternative 24,25 LE: 1b, GR: B.

However, available studies have demonstrated only equivalent clinical, but not microbiological, efficacy compared with ciprofloxacin.

As a result of increasing E. Co-amoxiclav is not recommended as a drug of first choice for empirical oral therapy of acute pyelonephritis LE: 4, GR: B.

Initial parenteral therapy in severe cases. In women whose pyelonephritis symptoms do not improve within 3 days, or resolve and then recur within 2 weeks, repeated urine culture and antimicrobial susceptibility tests and an appropriate investigation, such as renal ultrasound, CT or renal scintigraphy, should be performed LE: 4, GR: B.

In the patient with no urological abnormality, it should be assumed that the infecting organism is not susceptible to the agent originally used, and an alternative tailored treatment should be considered based on culture results LE: 4, GR: B.

For those patients who relapse with the same pathogen, the diagnosis of uncomplicated pyelonephritis should be reconsidered.

Figure 2. Antimicrobial prophylaxis: Antimicrobial prophylaxis for prevention of recurrent UTI should be considered only after counselling and behavioural modification has been attempted LE: 4, GR: A.

Continuous or postcoital antimicrobial prophylaxis should be considered to prevent recurrent uncomplicated cystitis in women in whom non-antimicrobial measures have been unsuccessful 35 LE: 1a, GR: A.

Drug regimens are shown in Tables 2. Its efficacy in other groups of patients, and its efficacy relative to antimicrobial prophylaxis remain to be established.

For other immunotherapeutic products on the market, larger phase III studies are still missing. Therefore, no recommendations are possible.

Only the specifically in studies tested Lactobacillus strains should be used for prophylaxis. Lactobacillus acidophilus and lactobacillus crispatus CTV05 strains are not available for prophylaxis.

Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC product is available as an orally administered capsule that has been used vaginally but not for UTI prophylaxis 39, Where commercially available, it is reasonable to consider the use of intravaginal probiotics that contain L.

Daily use of the oral product with strains GR-1 and RC is worth testing given that it can restore the vaginal lactobacilli, compete with urogenital pathogens, and prevent bacterial vaginosis, a condition that increases the risk of UTI 40 LE: 1b, GR: C.

The best approach is to use those compounds that have demonstrated clear bioactivity in urine. Recommended antibiotic regimens are shown in Table 2.

When indicated, ultrasonography or magnetic resonance imaging should be used preferentially to avoid radiation risk to the foetus LE: 4, GR: B.

No recommendation can be made with respect to screening for or treatment of bacteriuria in patients with neutropenia LE: 4.

Appendix 1. R elevant clinical trials of antimicrobial therapy of acute uncomplicated cystitis in adult nonpregnant women.

Study underpowered to show equivalence Ciprofloxacin SD 1 day Norfloxacin bid 3 days 1b Auquer 67 Ciprofloxacin as effective and tolerable as norfloxacin mg bid for 3 days.

Study underpowered for equivalence. Study underpowered to show equivalence. Fosfomycin trometamol SD 1 day Norfloxacin bid 5 days 1b De Jong 79 Fosfomycin as effective as norfloxacin but had significantly fewer adverse events.

Pefloxacin should be taken with meals to reduce gastrointestinal adverse events. In the abstract, number of patients and dose are missing.

R elevant clinical trials of therapy of acute uncomplicated pyelonephritis. Both treatment regimens after initial IV cefuroxime. Both treatment regimens after initial IV therapy.

Both studies refer to the same cohort. Meropenem 1 g tid? Side effects more common with 3 weeks treatment 0.

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Clinical practice. Acute uncomplicated urinary tract infection in women. N Engl J Med Jul 17; 3 Urinary tract infections.

In: Detection, prevention and management. Antibiotics versus placebo in the treatment of women with uncomplicated cystitis: a meta-analysis of randomized controlled trials.

J Infect Jul;64 1 Single-dose treatment of cystitis with fosfomycin trometamol Monuril : analysis of 15 comparative trials on 2, patients.

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Arch Intern Med Nov; 20 Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women.

Clin Infect Dis Oct;29 4 Int J Antimicrob Agents Jun;19 6 Quinolones for uncomplicated acute cystitis in women.

Infectious Diseases Society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults.

Clin Infect Dis Mar;40 5 Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med Jan; 1 Acute Pyelonephritis.

Evaluation of new anti-infective drugs for the treatment of UTI. Clin Infect Di, ; Comparison of ciprofloxacin 7 days and trimethoprim-sulfamethoxazole 14 days for acute uncomplicated pyelonephritis pyelonephritis in women: a randomized trial.

JAMA Mar; 12 Curr Med Res Opin Nov;23 11 Urology Jan;71 1 Fewer bacterial relapses after oral treatment with norfloxacin than with ceftibuten in acute pyelonephritis initially treated with intravenous cefuroxime.

Scand J Infect Dis ;33 5 International, prospective, randomized comparative study versus ciprofloxacin in general practice. Acute renal infection in women: treatment with trimethoprimsulfamethoxazole or ampicillin for two or six weeks.

A randomized trial. Ann Intern Med Mar; 3 Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology Jul;52 1 Treatment of complicated urinary tract infection in adults: combined analysis of two randomized, double-blind, multicentre trials comparing ertapenem and ceftriaxone followed by an appropriate oral therapy.

J Antimicrob Chemother Jun;53 Suppl 2:ii Empirical monotherapy with meropenem in serious bacterial infections. Meropenem Study Group.

Low-dosage cefepime as treatment for serious bacterial infections. Int J Antimicrob Agents Feb;19 2 Intravenous therapy with doripenem versus levofloxacin with an option to switch to oral therapy for the treatment of complicated lower urinary tract infection and pyelonephritis.

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BMJ Jun; A randomized trial to evaluate effectiveness and cost effectiveness of naturopathic cranberry products as prophylaxis against urinary tract infection in women.

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J Am Geriatr Soc Nov;38 11 Significance of asymptomatic bacteriuria in neurogenic bladder disease. Urology Apr;23 4 Candiduria: a randomized, double-blind study of treatment with fluconazole and placebo.

Clin Infect Dis Jan;30 1 Urinary tract infections following renal transplantation. Clin Transplant Nov;12 1 Amoxicillin-clavulanate vs ciprofloxacin for the treatment of uncomplicated cystitis in women: a randomized trial.

JAMA Feb; 8 Cefdinir versus cefaclor in the treatment of uncomplicated urinary tract infection. Clin Ther Jul;22 7 Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women.

Antimicrob Agents Chemother Mar;47 3 Cefuroxime axetil versus ofloxacin for short-term therapy of acute uncomplicated lower urinary tract infections in women.

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Clin Microbiol Infect Jan;8 1 Ciprofloxacin Urinary Tract Infection Group. Am J Med Mar; 3 A trial comparing low-dose, short-course ciprofloxacin and standard 7 day therapy with co-trimoxazole or nitrofurantoin in the treatment of uncomplicated urinary tract infection.

Short-course ciprofloxacin treatment of acute uncomplicated urinary tract infection in women. The minimum effective dose.

Arch Intern Med Mar; 5 : J Antimicrob Chemother Oct;54 4 Comparison of once-daily extended-release ciprofloxacin and conventional twice-daily ciprofloxacin for the treatment of uncomplicated urinary tract infection in women.

Clin Ther Dec;24 12 Efficacy and safety of a novel oncedaily extended-release ciprofloxacin tablet formulation for treatment of uncomplicated urinary tract infection in women.

Antimicrob Agents Chemother Oct;49 10 Single-dose enoxacin compared with 3-day treatment for urinary tract infection.

Antimicrob Agents Chemother Jun;33 6 Multicenter study of single-dose and multiple-dose fleroxacin versus ciprofloxacin in the treatment of uncomplicated urinary tract infections.

Fleroxacin in the treatment of uncomplicated urinary tract infections in women. Vienna, Austria. Jardin A. A general practitioner multicenter study: fosfomycin trometamol single dose versus pipemidic acid multiple dose.

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Single-dose fosfomycin trometamol Monuril versus multiple-dose norfloxacin: results of a multicenter study in females with uncomplicated lower urinary tract infections.

Urol Int ;46 4 Fosfomycin trometamol in a single dose versus seven days nitrofurantoin in the treatment of acute uncomplicated urinary tract infections in women.

Pharm World Sci Dec;15 6 Analyse de 15 essais comparatifs portant sur malades. A comparison between single-dose fosfomycin trometamol Monuril and a 5-day course of trimethoprim in the treatment of uncomplicated lower urinary tract infection in women.

Int J Antimicrob Agents Apr;10 1 Comparison of single-dose fosfomycin and a 7-day course of nitrofurantoin in female patients with uncomplicated urinary tract infection.

Clin Ther Nov;21 11 Fosfomycin tromethamine in uncomplicated urinary tract infections: a clinical study.

Chemotherapy May;51 Single-dose fluoroquinolone therapy of acute uncomplicated urinary tract infection in women: results from a randomized, doubleblind, multicenter trial comparing single-dose to 3-day fluoroquinolone regimens.

Urology Mar;59 3 Gatifloxacin mg as a single shot or mg once daily for 3 days is as effective as ciprofloxacin mg twice daily for the treatment of patients with uncomplicated urinary tract infections.

Int J Antimicrob Agents Jun;23 6 A double-blind, randomised trial of the efficacy and safety of short-course, once-daily levofloxacin versus ofloxacin twice daily in uncomplicated urinary tract infection.

Infectious Diseases in Clinical Practice, Ch 9: pp. Short-course levofloxacin mg qid vs ofloxacin mg bid in uncomplicated UTI: a double-blind, randomized trial.

Lomefloxacin versus norfloxacin in the treatment of uncomplicated urinary tract infections: three-day versus seven-day treatment. Scand J Infect Dis ;24 6 Treatment of acute uncomplicated urinary tract infections with 3 days of lomefloxacin compared with treatment with 3 days of norfloxacin.

Antimicrob Agents Chemother Mar;37 3 Br J Clin Pharmacol Aug;58 2 Nitrofurantoin modified release versus trimethoprim or co-trimoxazole in the treatment of uncomplicated urinary tract infection in general practice.

Double-blind comparison of 3-day versus 7-day treatment with norfloxacin in symptomatic urinary tract infections. Scand J Infect Dis ;20 6 Three-day versus seven-day treatment with in acute cystitis.

Curr Ther Res ; Efficacy and safety of norfloxacin mg once-daily versus norfloxacin mg twice-daily in the treatment of uncomplicated urinary tract infections in women: a double-blind, randomized clinical trial.

J Chemother Apr;10 2 Ofloxacin versus trimethoprim-sulphamethoxazole in acute cystitis. Drugs ;34 Suppl Ofloxacin versus trimethoprim-sulfamethoxazole for treatment of acute cystitis.

Antimicrob Agents Chemother Aug;33 8 Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women.

Antimicrob Agents Chemother Jul;35 7 Pefloxacin single-dose in the treatment of acute uncomplicated lower urinary tract infections in women: a meta-analysis of seven clinical trials.

Int J Antimicrob Agent, Aug;4 3 Quinolones for short-term treatment of uncomplicated urinary tract infection.

East Afr Med , ;76 10 Comparison of pivmecillinam and cephalexin in acute uncomplicated urinary tract infection. Int J Antimicrob Agents Jan;13 3 Three days of pivmecillinam or norfloxacin for treatment of acute uncomplicated urinary infection in women.

Scand J Infect Dis ;34 7 Symptomatic vaginal candidiasis after pivmecillinam and norfloxacin treatment of acute uncomplicated lower urinary tract infection.

Int J Antimicrob Agents Oct;20 4 Clinical and bacteriological outcome of different doses and duration of pivmecillinam compared with placebo therapy of uncomplicated lower urinary tract infection in women: the LUTIW project.

Randomized, double-blind comparison of single-dose regimens of rufloxacin and pefloxacin for acute uncomplicated cystitis in women.

Antimicrob Agents Chemother Jan;39 1 Treatment of community-acquired acute uncomplicated urinary tract infection with sparfloxacin versus ofloxacin.

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Curr Therap Res Clin Exp ; A clinical comparison between Macrodantin and trimethoprim for prophylaxis in women with recurrent urinary infections.

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J Urol Dec; 6 The incidence of UTI varies depending on age and sex. In the first year of life, mostly the first 3 months, UTI is more common in boys 3.

Paediatric UTI is the most common cause of fever of unknown origin in boys less than 3 years. The clinical presentation of a UTI in infants and young children can vary from fever to gastrointestinal, lower or upper urinary tract symptoms.

The objective is to rule out the unusual occurrence of obstruction, vesicoureteric reflux VUR and dysfunctional voiding, e.

Chronic pyelonephritic renal scarring develops very early in life due to the combination of a UTI, intrarenal reflux and VUR. It sometimes arises in utero due to dysplasia.

Although rare, renal scarring may lead to severe long-term complications such as hypertension and chronic renal failure.

Vesicoureteric reflux is treated with long-term prophylactic antibiotics GR: B. Surgical re-implantation or endoscopic treatment is reserved for the small number of children with breakthrough infection GR: B.

In the treatment of a UTI in children, short courses are not advised and therefore treatment is continued for days and longer GR: A.

If the child is severely ill with vomiting and dehydration, hospital admission is required and parenteral antibiotics are given initially GR: A.

It represents the most common bacterial infection in children less than 2 years of age 1 LE: 2a. The outcome of a UTI is usually benign, but in early infancy it can progress to renal scarring, especially when associated with congenital anomalies of the urinary tract.

Delayed sequelae related to renal scarring include hypertension, proteinuria, renal damage and even chronic renal failure, requiring dialysis treatment in a significant number of adults 2 LE: 2a.

The incidence is different for children under 3 months of age, when it is more common in males. The incidence of asymptomatic bacteriuria is 0.

The incidence of symptomatic bacteriuria is 0. Hospital-acquired infections show a wider pattern of aggressive organisms, such as Klebsiella, Serratia and Pseudomonas spp.

Groups A and B streptococci are relatively common in the newborn 6. There is an increasing trend towards the isolation of Staphylococcus saprophyticus in UTIs in children, although the role of this organism is still debatable 7.

Retrograde ascent is the most common mechanism of infection. Nosocomial infection and involvement as part of a systemic infection are less common 8.

Obstruction and dysfunction are among the most common causes of urinary infection. Enterobacteria derived from intestinal flora colonize the preputial sac, glandular surface and the distal urethra.

Among these organisms are strains of E. A wide variety of congenital urinary tract abnormalities can cause UTIs through obstruction, e. More mundane but significant causes of UTIs include labial adhesion and chronic constipation 7.

Dysfunctional voiding in an otherwise normal child may result in infrequent bladder emptying aided by delaying manoeuvres, e.

Neuropathic bladder dysfunction spina bifida, sphincter dyssynergia, etc may lead to postvoid residual urine and secondary VUR 4.

The link between renal damage and UTIs is controversial. The mechanism in obstructive nephropathy is self-evident, but more subtle changes occur where there is VUR.

These must all work together in early childhood when the growing kidney is likely to be susceptible to parenchymal infection.

Later on in childhood, the presence of bacteriuria seems irrelevant to the progression of existing scars or the very unusual formation of new scars.

Another confounding factor is that many so-called scars are dysplastic renal tissue which developed in utero Epididymoorchitis is extremely unusual.

With scrotal pain and inflammation in a boy, testicular torsion has to be considered. A UTI in neonates may be non-specific and with no localization.

In small children, a UTI may present with gastrointestinal signs, such as vomiting and diarrhoea. In the first weeks of life, Rarely, septic shock will be the presentation.

Signs of a UTI may be vague in small children, but later on, when they are older than 2 years, frequent voiding, dysuria and suprapubic, abdominal or lumbar pain may appear with or without fever.

From the clinical point of view, severe and simple forms of UTIs should be differentiated because to some extent the severity of symptoms dictates the degree of urgency with which investigation and treatment are to be undertaken Table 3.

Table 3. The child is only slightly or not dehydrated and has a good expected level of compliance. When a low level of compliance is expected, such a child should be managed as one with a severe UTI.

The absence of fever does not exclude the presence of an infective process. Urine must be obtained under bacteriologically reliable conditions when undertaking a urine specimen culture The urine specimen may be difficult to obtain in a child less than 4 years old and different methods are advised since there is a high risk of contamination 17, In order to obtain a urine sample in the best condition in children under 2 years of age girls and uncircumcised boys without sphincteric control , it is better to use suprapubic bladder aspiration or bladder catheterization.

In older children with sphincteric control, midstream urine MSU collection is possible and reliable The presence of pyuria more than 5 leucocytes per field and bacteriuria in a fresh urine sample will reinforce the clinical diagnosis of UTI In these cases, it is better to repeat the culture or to evaluate the presence of other signs, such as pyuria, nitrites or other biochemical markers When an infection is caused by Gram-positive bacteria, the test may be negative 8, A combination of nitrite and leucocyte esterase testing improves sensitivity and specificity, but carries the risk of false-positive results The dipstick test has become useful to exclude rapidly and reliably the presence of a UTI, provided both nitrite and leucocyte esterase tests are negative.

If the tests are positive, it is better to confirm the results in combination with the clinical symptoms and other tests 17, In such cases, it is advisable to repeat the urinalysis after 24 hours to clarify the situation.

Even in febrile children with a positive urine culture, the absence of pyuria may cast doubt on the diagnosis of UTI.

Instead, asymptomatic bacteriuria with a concomitant septic focus responsible for the febrile syndrome has to be considered.

Bacteriuria without pyuria is found in 0. This figure corresponds well with the estimated rate of asymptomatic bacteriuria in childhood 20, 22 LE: 2a.

Chlamydia trachomatis. Thus, either bacteriuria or pyuria may not be considered reliable parameters to diagnose or exclude UTI. Their assessment can be influenced by other factors, such as the degree of hydration, method of specimen collection, mode of centrifugation, volume in which sediment is resuspended and subjective interpretation of results However, according to Landau et al.

For all of these reasons, in neonates and children under 6 months of age, either pyuria, bacteriuria or the nitrite test, separately, have minimal predictive value for UTI 25,26 LE: 3.

Current techniques do not fulfil all such requirements. It is subjective and therefore operator-dependent, and gives no information on renal function.

However, scars can be identified, although not as well as with technetiumm dimercaptosuccinic acid Tcm DMSA scanning 29,30 LE: 2a.

This technique has been shown to be very sensitive and excretory urography must be reserved only for when images need to be morphologically clarified 31 LE: 2a.

This technique is helpful in determining functional renal mass and ensures an accurate diagnosis of cortical scarring by showing areas of hypoactivity indicating lack of function.

A UTI interferes with the uptake of this radiotracer by the proximal renal tubular cells, and may show areas of focal defect in the renal parenchyma.

A star-shaped defect in the renal parenchyma may indicate an acute episode of pyelonephritis. A focal scarring or a smooth uniform loss of renal substance as demonstrated by Tcm DMSA has generally been regarded as being associated with VUR reflux nephropathy 35, However, Rushton et al.

Minimal parenchymal defects, when characterized by a slight area of hypoactivity, can resolve with antimicrobial therapy 39, However, defects lasting longer than 5 months are considered to be renal scarring 41 LE: 2a.

Tcm DMSA scans are considered more sensitive than excretory urography and ultrasonography in the detection of renal scars It remains questionable whether radionuclide scans could substitute for echography as a first-line diagnostic approach in children with a UTI 46, It is considered mandatory in the evaluation of UTIs in children less than 1 year of age.

Its main drawbacks are the risk of infection, the need for retrogrades filling of the bladder and the possible deleterious effect of radiation on children In recent years, tailored low-dose fluoroscopic VCU has been used for the evaluation of VUR in girls in order to minimize radiological exposure Voiding cystourethrography is mandatory in the assessment of febrile childhood UTI, even in the presence of normal ultrasonography.

It represents an attractive alternative to conventional cystography, especially when following patients with reflux, because of its lower dose of radiation.

Disadvantages are a poor image resolution and difficulty in detecting lower urinary tract abnormalities 51, Further studies are necessary to determine the role of this new imaging modality in UTI.

The major disadvantages in infants are the risks of side effects from exposure to contrast media and radiation However, the role of excretory urography is declining with the increasing technical superiority of CT 54 and MRI.

However, the indications for their use is still limited in UTI. Only a minority of children with a UTI have an underlying urological disorder, but when present such a disorder can cause considerable morbidity.

Thus, after a maximum of two UTI episodes in a girl and one episode in a boy, investigations should be undertaken Figure 3.

Figure 3. Antimicrobial treatment has to be initiated on an empirical basis, but should be adjusted according to culture results as soon as possible.

In patients with an allergy to cephalosporins, aztreonam or gentamicin may be used. When aminoglycosides are necessary, serum levels should be monitored for dose adjustment.

Chloramphenicol, sulphonamides, tetracyclines, rifampicin, amphotericin B and quinolones should be avoided.

The use of ceftriaxone must also be avoided due to its undesired side effect of jaundice. A wide variety of antimicrobials can be used in older children, with the exception of tetracyclines because of teeth staining.

Fluorinated quinolones may produce cartilage toxicity 58 , but if necessary may be used as second-line therapy in the treatment of serious infections, since musculoskeletal adverse events are of moderate intensity and transient 60, For a safety period of hours, parenteral therapy should be administered.

This provides some advantages, such as less psychological impact on the child and more comfort for the whole family. It is also less expensive, well tolerated and eventually prevents opportunistic infections However, the indication for TMP is declining in areas with increasing resistance.

UPDATE APRIL 39 In children less than 3 years of age, who have difficulty taking oral medications, parenteral treatment for days seems advisable, with similar results to those with oral treatment If there are significant abnormalities in the urinary tract e.

VUR, obstruction , appropriate urological intervention should be considered. If renal scarring is detected, the patient will need careful follow-up by a paediatrician in anticipation of sequelae such as hypertension, renal function impairment and recurrent UTI.

An overview of the treatment of febrile UTIs in children is given in Figure 3. Treatment of febrile UTIs in children. A single parenteral dose may be used in cases of doubtful compliance and with a normal urinary tract 66 LE: 2a.

If the response is poor or complications develop, the child must be admitted to hospital for parenteral treatment It may also be used after an acute episode of UTI until the diagnostic work-up is completed.

The most effective antimicrobial agents are: nitrofurantoin, TMP, cephalexin and cefaclor Jodal U. The natural history of bacteriuria in childhood.

Development of hypertension and uraemia after pyelonephritis in childhood: 27 year follow up. BMJ Sep; Voiding dysfunction in children. Urol Clin North Am Aug;31 3 , ix.

Infections of the urinary tract. Pediatr Infect Dis J Feb;11 2 Nosocomial infections in pediatric intensive care units in the United States.

National Nosocomial Infections Surveillance System. Pediatrics Apr; 4 :e Staphylococcus saprophyticus urinary tract infections in children.

Eur J Pediatr Jan; 1 Urinary tract infection in children: etiology and epidemiology. Urol Clin North Am Aug;31 3 , ix-x.

Effect of circumcision on incidence of urinary tract infection in preschool boys. J Pediatr Jan; 1 Cohort study on circumcision of newborn boys and subsequent risk of urinary-tract infection.

Lancet Dec; Adherence of bacteria to human foreskins. J Urol Nov; 5 Toilet habits of children evaluated for urinary tract infection.

J Urol Aug; 2 Pt 2 The characteristics of primary vesico-ureteric reflux in male and female infants with pre-natal hydronephrosis.

Br J Urol Aug;80 2 Urinary tract infection in febrile infants younger than eight weeks of Age.

Pediatrics Feb; 2 :E Diagnosis and management of pediatric urinary tract infections. Clin Microbiol Rev Apr 2 Pediatric urinary tract infection.

Urinary tract infection in children: pathophysiology, risk factors and management. Infect Med ; Hoberman A, Wald ER.

Urinary tract infections in young febrile children. Pediatr Infect Dis J Jan;16 1 The urine dipstick test useful to rule out infections.

A meta-analysis of the accuracy. BMC Urol Jun; Spontaneous clearance of asymptomatic bacteriuria in infants. Acta Paediatr Scand Mar;79 3 Measurement of pyuria and its relation to bacteriuria.

Am J Med Jul;75 1B The value of urinalysis in differentiating acute pyelonephritis from lower urinary tract infection in febrile infants.

Pediatr Infect Dis J Sep;13 9 Prevalence of urinary tract infection in febrile infants. J Pediatr Jul; 1 Diagnosis and management of urinary tract infections.

Curr Opin Urol Feb; Urinary N-acetylbetaglucosaminidase and betamicroglobulin in the diagnosis of urinary tract infection in febrile infants.

Pediatr Infect Dis J Apr;13 4 Interleukin 6 response to urinary tract infection in childhood. Pediatr Infect Dis J Jul;13 7 The sensitivity of renal scintigraphy and sonography in detecting nonobstructive acute pyelonephritis.

Sonographic measurement of renal enlargement in children with acute pyelonephritis and time needed for resolution: implications for renal growth assessment.

Urinary tract infection in infants and children evaluated by ultrasound. Radiology Feb; 2 Imaging in acute pyelonephritis.

Curr Opin Urol Jan; Vesico-ureteric reflux in the damaged non-scarred kidney. Pediatr Nephrol Jan;6 1 Renal radionuclide studies.

Textbook of genitourinary surgery.

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