URINARY TRACT INFECTIONS Mark Schuster, M.D., Ph.D.

Transcription

1 URINARY TRACT INFECTIONS Mark Schuster, M.D., Ph.D. This review is based on textbooks of pediatrics (Roth and Gonzales in Oski et al., 1994), pediatric primary care ( ), and pediatric infectious disease (Marks and Arrieta in Feigin and Cherry, 1992). Several articles were also identified from the textbook bibliographies and from a MEDLINE search of English-language review articles on urinary tract infections (UTIs) and pyelonephritis in pediatric age groups published between January 1990 and March IMPORTANCE The urinary tract ranks second only to the upper respiratory tract as a source of morbidity from bacterial infection in children (Roth and Gonzales in Oski et al., 1994). About one percent of boys and three percent of girls will have had a symptomatic UTI by their eleventh birthday (Stull and LiPuma, 1991). Most UTIs are successfully treated without significant sequelae (Zelikovic et al., 1992). However, vesicoureteral reflux (VUR) of infected urine into the renal parenchyma (also known as reflux nephropathy) can cause renal scarring. Reflux-associated scarring is the most common single cause of renal hypertension and chronic renal failure in children (White, 1990); it can also cause growth failure. Once renal scarring has occurred, no remedial or preventive measures can be taken (Treves, 1994). Up to 50 percent of children younger than five years old who have UTI and fever (which is common with UTI) also have VUR, and over 80 percent of children younger than five years old who have recurrent UTI and persistent VUR develop renal scarring ( ). Most renal scars seem to appear before five years old, though new scar formation and progression of scarring have been shown in older children (Andrich and Majd, 1992). Timely identification of acute infection, appropriate treatment, detection of patients at risk for renal scarring, and prevention of recurrent infection can greatly reduce

2 the risk of an adverse outcome ( ). UTI management thus has two primary aims: the relief of symptoms and the prevention of renal damage (White, 1990). EFFICACY AND/OR EFFECTIVENESS OF INTERVENTIONS Screening There is no consensus on whether asymptomatic children should be screened routinely for bacteriuria (bacteria in the urine). Kemper and Avner (1992) make the case that because of high costs and false positive rates, routine screening of asymptomatic preschool children with urinalysis (UA) should not be done. Diagnosis Infants with a UTI may have nonspecific symptoms such as fever, irritability, and other signs of systemic illness, including failure to thrive, vomiting, and diarrhea. Signs of bladder obstruction such as abdominal distention, weak or threadlike urinary stream, infrequent voiding, and discolored or malodorous urine may be present ( ). Decreased feeding, lethargy, jaundice, hepatomegaly, and splenomegaly may also be present. A child with UTI may also be asymptomatic (Lebel in Oski et al., 1994). Febrile infants without an apparent source of fever should be evaluated for UTI (Stull and LiPuma, 1991). UTIs are diagnosed in 7.5 percent of infants less than two months who have fever (Lebel in Oski et al., 1994). Infants with UTI should be evaluated for other potential sources of infection with examination of blood and cerebrospinal fluid (Sherbotie and Cornfeld, 1991; Lebel in Oski et al., 1994). Preschool children may complain of voiding discomfort, or they may develop recurrent (secondary) enuresis, in addition to fever and abdominal or flank pain. School-age children typically have "classic" signs and symptoms of UTI, including dysuria, frequency, urgency, abdominal or flank pain, and fever ( ). Hematuria may occur with UTI (Marks and Arrieta in Feigin and Cherry, 1992a). An association between sexual abuse and UTIs has been proposed but has not been demonstrated (Stull and LiPuma, 1991).

3 Diagnosis is made by urine culture. A midstream clean-catch urine specimen may be used if the child is toilet-trained. If not, urine may be obtained by percutaneous bladder tap or urethral catheterization. In addition, a urine bag collection is adequate if the culture is negative; however, a positive culture could result from a contaminant from the rectum, skin, or prepuce, so it must be confirmed by one of the other two methods (Roth and Gonzales in Oski et al., 1994; ). Urine cultures from bags may sometimes be so suggestive of UTI that some physicians might believe it is unnecessary to collect a more reliable culture, particularly since antibiotic therapy does not present much risk. However, the radiologic work-up (discussed below) is quite invasive and so treatment based on bag urine cultures should be the exception rather than the rule. The culture must be obtained before antibiotics are given because a single dose prior to urine collection can lead to a false-negative result (Roth and Gonzales in Oski et al., 1994). Bacterial colony counts greater than 100,000 colonies/ml urine for a single organism should be interpreted as diagnostic of a UTI. Colony counts of 10,000 to 100,000 colonies/ml urine associated with clinical signs and symptoms are suggestive of a UTI, but a repeat culture should be done (this may not always be possible if the patient has already started antibiotics). Colony counts less than 10,000/ml may be considered positive if the organism is staphylococcus or a fungus or if the patient has an indwelling catheter. Any bacterial growth from a suprapubic aspirate should be considered positive (Marks and Arrieta in Feigin and Cherry, 1992a). Though urinalysis may be used to screen for possible UTI (Woodhead in ), a positive urinalysis must be confirmed with a culture in order to make the diagnosis. UTIs can be subdivided into two categories based on anatomical location: lower tract infection (cystitis) and upper tract infection (pyelonephritis) (Zelikovic et al., 1992). It can be difficult to distinguish between the two in children. Dysuria, frequency, urgency, enuresis, suprapubic pain, and a low-grade fever are more common in cystitis, whereas high fever, nausea, vomiting, flank pain, and lethargy

4 are usually associated with acute pyelonephritis. Overlap in symptoms occurs often (Roth and Gonzales in Oski et al., 1994) and can make specific diagnosis difficult. Andrich and Majd (1992) say that clinical and laboratory findings are not adequate to diagnose pyelonephritis, and therefore argue for performing renal cortical scintigraphy (RCS) with DMSA (dimercaptosuccinic acid) or GHA (glucoheptonate) in all patients with a febrile UTI, especially young children who are particularly susceptible to scarring. RCS is recommended during the first 2-3 days if the child is hospitalized and within the first 2-3 weeks if the child is treated as an outpatient. However, this is not a typical recommendation of pediatric textbooks, and we have found no analysis weighing the costs and benefits of performing RCS on all children with a UTI. Standard clinical practice remains presumptive treatment of all young children with a UTI for pyelonephritis. Treatment Infants with UTI are at risk of developing serious sequelae, including sepsis, electrolyte abnormalities, and shock. They should be treated with parenteral antibiotics. A repeat urine culture should be obtained after 48 hours to assure that urine has been sterilized (Sherbotie and Cornfeld, 1991; Lebel in Oski et al., 1994). Parenteral antibiotic therapy should be continued in infants for 5-7 days. If the baby has improved clinically after 3-5 afebrile days and has sterile urine, antibiotics may be given orally to complete a day course. For ill-appearing patients and those with genitourinary abnormalities and pyelonephritis, at least 7 days of parenteral antibiotics are recommended, followed by prolonged oral antimicrobial therapy (e.g., 2-3 weeks) once clinical improvement and microbiologic cure are documented (Sherbotie and Cornfeld, 1991). If the child is not afebrile within 1-2 days or if the repeat urine culture is positive, the child needs an immediate evaluation for urologic obstruction or abscess (in addition to reconfirming bacterial antibiotic susceptibilities) (see radiologic work-up below) (Lebel in Oski et al., 1994).

5 A repeat culture should be obtained 2-3 days after the start of standard 10-day therapy or 3-4 days after completion of short-course therapy. Sterile urine demonstrates antibiotic effectiveness. If urine is not sterile or the patient remains symptomatic, another urine specimen should be sent for bacterial identification and susceptibility testing and a broad-spectrum antibiotic should be prescribed. Urine should be recultured 3 days later to confirm effectiveness ( ). Any child with symptomatic pyelonephritis should be managed in hospital with parenteral antibiotics ( ). Other children can be treated adequately on an outpatient basis with a 7-10 day course. A higher recurrence rate occurs with shorter courses of antibiotics (Roth and Gonzales in Oski et al., 1994). A broadspectrum antibiotic is used initially (Roth and Gonzales in Oski et al., 1994; ). It must be changed if the organism is not sensitive to it. Treatment for 10 days is adequate ( ). Some clinicians believe that bacterial identification and determination of antibiotic susceptibilities are not necessary in most uncomplicated UTIs. Because most UTIs are caused by E. coli (a type of bacteria) sensitive to commonly used antibiotics, rapid clinical response to treatment and a negative culture 2-4 days after initiation of treatment serve the same ends as sensitivity testing. However, the patient with systemic toxicity at initial presentation or who fails to respond promptly to treatment should have these done ( ). Follow-up Care Recommendations for follow-up culture (to document eradication of infection) are quite variable, ranging from one week after completion of therapy (Roth and Gonzales in Oski et al., 1994) to one month afterwards or just before radiologic evaluation ( ). Woodhead (in ) recommends further follow-up every three months for one year and then annually for 2-3 years. However, others do not mention such persistent follow-up.

6 Prophylaxis Children with at least four UTIs per year should receive daily prophylactic low-dose antibiotics for 9-12 months (Roth and Gonzales in Oski et al., 1994). Woodhead (in ) recommends prophylaxis for 6 months. Lebel (in Oski et al., 1994) also recommends prophylaxis for recurrent UTIs. Because the length of prophylaxis is open to debate, the shorter time period (6 months) will be used for an indicator. Any child who needs a radiologic study for VUR should receive low dose prophylactic antibiotics until the voiding cystourethrogram (VCUG) has been done ( ). Radiologic Studies There is consensus that some children with UTIs need to have a radiologic work-up, but there is disagreement over the particulars of which ages and which genders need what type of work up. Work-up is recommended for all boys (Roth and Gonzales in Oski et al., 1994; ; Sherbotie and Cornfeld, 1991; Gillenwater, 1991). Andrich and Majd (1992) specify that it is necessary only for boys less than 10 years old. There is less consensus for girls, with recommendations including: girls less than 3 years old or girls older than 3 with systemic toxicity, recurrent UTIs, or failure of infection to respond promptly to therapy ( ); girls less than 5 years old, girls with evidence of genitourinary abnormalities, and girls older than 5 with recurrent symptomatic bacteriuria (Sherbotie and Cornfeld, 1991); girls less than 10 years old, girls who fail to respond to antibiotic therapy, and girls with recurrent UTIs (Andrich and Majd, 1992); all girls (Gillenwater, 1991). Given these disagreements, our indicators for radiologic work-ups cover all boys less than 10 years old, all girls less than 3 years old, and any other children who require hospitalization (as a proxy for systemic toxicity). There are several radiographic studies that can be done to evaluate urinary tract anatomy and function. Recommendations for which studies to use vary. Roth and Gonzales (in Oski et al., 1994) recommend (1)

7 VCUG and (2) renal ultrasound (RUS), intravenous pyelogram (IVP), or nuclear medicine renal scan, though they say the VCUG is not necessary for the older girl with simple cystitis. Woodhead (in ) recommends (1) VCUG or radionuclide cystogram and (2) IVP or RUS. Gillenwater (1991) recommends (1) radionuclide or contrast cystograms and (2) RUS or intravenous urograms. Andrich and Majd (1992) recommend (1) VCUG in boys and isotope cystogram (IC) or VCUG in girls and (2) RUS for afebrile, nontoxic-appearing children. If the cystogram is positive, RCS should be done to see if there is evidence of previous unsuspected renal parenchymal infection. If RUS shows hydronephrosis, diuretic renography (with DTPA or MAG3) must be done to determine if it is obstructive or nonobstructive (Andrich and Majd, 1992). Our indicators accept any of several options for radiologic workup: (1) VCUG for boys and IC or VCUG in girls, and (2) RUS, IVP, or nuclear medicine renal scan. A key concern is the amount of radiation exposure from these various methods. IC may be preferred for girls under 5 because of the lower radiation exposure as compared to VCUG and concerns about effect on the ovaries. Similarly, IVP has higher levels of radiation exposure than the other tests and may not provide enough additional information to justify the increased risk. This review does not address recommendations for further work-up and treatment following these radiologic studies. There are variable recommendations for how long after diagnosis the VCUG (or IC) should be done, ranging from a few days or as soon as the patient is asymptomatic (Andrich and Majd, 1992) to 4-6 weeks after the infection has been treated ( ). Our indicator accepts any time within the first three months after diagnosis, as long as the patient has been on prophylactic antibiotics from completion of the treatment regimen until the time of the VCUG or IC. If the symptoms with each recurrence remain consistent with cystitis, there is no need for repeated invasive evaluations. However, for the child with a persistent problem with UTIs, it seems prudent to repeat a renal ultrasound every 2-3 years to document normal renal growth (Roth and Gonzales in Oski et al., 1994).

8 Reflux and Other Abnormalities There is consensus that children with VUR need prophylactic antibiotics until the reflux resolves ( ; Andrich and Majd; Gillenwater, 1991). Lebel (in Oski et al., 1994) specifies that children with Grade II or higher reflux need prophylaxis. In addition, Andrich and Majd raise the idea that any child whose RCS shows renal parenchymal involvement should be considered for prophylaxis as well (Andrich and Majd, 1992). However, neither doing RCS nor prophylaxing all children with a positive RCS has become a standard of practice. When VUR is diagnosed, it must be evaluated yearly with VCUG or radionuclide cystogram. There should be monitoring of renal growth with US or IVP as long as VUR persists. Low-grade VUR resolves spontaneously in almost 80 percent of cases and urologic evaluation is unnecessary unless VUR is complicated by poor growth, hypertension, or reduced renal function ( ). Andrich and Majd prefer IC to minimize radiation exposure. Infants with reflux should have RUS and VCUG or radionuclide scan repeated in 6-12 months (Lebel in Oski et al., 1994). Higher grades of reflux do not spontaneously resolve and indicate more severe urinary tract damage. Patients with high grade VUR should have urologic evaluation and almost always require urethral reimplantation ( ; Gillenwater, 1991), although exact management is controversial (White, 1990; O'Donnell, 1990). Optimal treatment for moderate degrees of reflux has not been established (Gillenwater, 1991). Infants with obstructive signs (e.g., midline lower abdominal distention; flank mass; infrequent or prolonged voiding; weak, dribbling, or threadlike urinary stream; or ballooning of the penile urethra) must be evaluated by a pediatric urologist. Children with any degree of VUR with hypertension, growth retardation, reduced renal function, anemia, or other structural renal abnormalities should also have urologic evaluation ( ). Asymptomatic siblings of children with VUR require screening because up to 45 percent will also have VUR compared to less than one

9 percent of the general population (Andrich and Majd, 1992). Andrich and Majd (1992) prefer IC to limit radiation but acknowledge that some radiologists will find the VCUG more reliable because they perform it more often.

10 RECOMMENDED QUALITY INDICATORS FOR URINARY TRACT INFECTION The following criteria apply to urinary tract infections for infants and children. Diagnosis Indicator 1. If an infant or child presents with any of the following symptoms/signs,* either a urine culture should be performed or a urinalysis should be performed; if urinalysis is positive, a urine culture should be performed: a. malodorous urine, abnormal urinary stream, or change in urinary stream in an infant or child; b. failure to thrive in an infant or child; c. vomiting associated with fever in an infant; d. jaundice associated with fever in a neonate; e. pain/discomfort with urination (dysuria), frequency, urgency, flank pain (unrelated to trauma) in a child; f. hematuria unrelated to trauma in infant or child; or g. secondary enuresis in a child. 2. In order to diagnose UTI, a positive culture from one of the following methods of urine collection is necessary: bladder tap, or catheterization, or clean catch. 3. In order to rule out UTI, a negative UA or culture from one of the following methods of urine collection is necessary: bladder tap, or catheterization, or clean catch, or urine bag. 4. If the culture shows greater than 100,000 colonies/ml urine of a single organism, then the patient should be diagnosed and treated for UTI. Quality of evidence Literature Benefits Comments Marks and Arietta in Feigin and Cherry, 1992a; ; Lebel in Oski et al., 1994 Roth and Gonzales in Oski et al., 1994; Roth and Gonzales in Oski et al., 1994; Marks and Arrieta in Feigin and Cherry, 1992a Prevent Prevent scarring and renal hypertension. Prevent allergic reactions from antibiotics. Prevent complications of invasive procedures. Prevent allergic reactions from antibiotics. Prevent complications of invasive procedures. Prevent allergic reactions from antibiotics. Prevent complications of invasive radiologic procedures. Prevent Prevent renal scarring and hypertension. Without proper diagnosis, an untreated UTI in children can cause complications, including vesicoureteal reflux of infected urine (which can lead to renal scarring, which can cause renal hypertension and chronic renal failure). Of note, the sources used in this review sometimes distinguish between infants and children without specifying the age cut-off between them. We will define infants as children who have not reached their first birthday. Bag urine collection has a high false positive rate. False positives are not trivial, not only because of inappropriate antibiotic usage but also because of potential complications of radiologic procedures discussed below. Bag urine collection has a high false positive rate. False positives are not trivial, not only because of inappropriate antibiotic usage but also because of potential complications of radiologic procedures discussed below. 360

11 5. If there is bacterial growth of a single organism with at least 10,000 colonies/ml urine from a catherized specimen, then UTI should be diagnosed and treated. 6. Growth of 10,000 to 100,000 colonies/ml urine from clean catch should be followed up with a repeat urine culture if the patient has not already been treated. 7. If there is any bacterial growth from a specimen obtained from a bladder tap then a UTI should be diagnosed and treated. 8. Urine culture must be obtained by clean catch, catheterization, or bladder tap before antibiotics are given. Marks and Arrieta in Feigin and Cherry, 1992a Marks and Arrieta in Feigin and Cherry, 1992a Marks and Arrieta in Feigin and Cherry, 1992a Roth and Gonzales in Oski et al., 1994 Prevent allergic reactions from antibiotics. Prevent complications of invasive radiologic procedures. Prevent Prevent renal scarring and hypertension. Prevent allergic reactions from antibiotics. Prevent complications of invasive radiologic procedures. Prevent Prevent renal scarring and hypertension. Prevent pyelonephritis. Prevent allergic reactions from antibiotics. Prevent pyelonephritis. Prevent chronic renal failure. Prevent renal hypertension. Avoid invasive radiologic work-up. Specimens from clean catch and catheter collection are less likely to have contaminants. This is a borderline result that may be due to contamination or infection. Repeat culture helps determine whether there is true infection. A bladder tap specimen is unlikely to have a contaminant. Pre-antibiotic culture allows determination of whether the patient actually has a UTI. It also allows determination of antibiotic sensitivities, which enables switching to proper treatment if necessary. There may be extenuating circumstances where antibiotics cannot wait for culture. For example, a child may have strong evidence of meningococcal sepsis but clinicians may be unsuccessful in obtaining a urine sample. This child will need antibiotics immediately. However, such situations should be uncommon and distributed randomly among sites, so that they will not need to be accounted for at present. 361

12 Treatment Indicator 9. All infants with a diagnosis of UTI must initially receive intravenous antibiotics. 10. IV antibiotics may be switched to oral antibiotics if the infant has had at least 3 days without fever, a negative repeat urine culture, and negative blood and CSF culture. 11. Infants with UTI should receive a total of at least 10 days of antibiotics (IV and oral). 12. Infants with UTI should have a repeat urine culture between 48 hours and the end of the fifth day of IV therapy. 13. Children with UTI and systemic symptoms such as hypotension, poor perfusion, anorexia, or emesis, should be treated initially with IV antibiotics. 14. If the child is being treated with oral antibiotics, by the fourth day, either (1) antibiotic sensitivities must be determined, or (2) a repeat culture must be sent. 15. When antibiotic sensitivities are checked, if the organism is not sensitive to the antibiotic, the antibiotic should be switched to one to which the organism is sensitive within 1 day. 16. All children with the diagnosis of UTI should receive at least 7 days of antibiotics. 17. All children with the diagnosis of pyelonephritis should be treated initially with IV antibiotics. 18. A child with four UTIs in a single year should receive prophylactic antibiotics for at least six months. Quality of evidence Literature Benefits Comments Sherbotie and Cornfeld, 1991 Sherbotie and Cornfeld, 1991 Sherbotie and Cornfeld, 1991 Sherbotie and Cornfeld, 1991 Inferred from Roth and Gonzales in Oski et al., 1994 IV antibiotics are more likely than oral antibiotics to be effective in infants. Once it is clear the infection is under control, it is safe to switch to oral antibiotics. Once it is clear the infection is under control, it is safe to switch to oral antibiotics. Sherbotie and Cornfeld recommend the repeat culture after 48 hours, but do not give a deadline for the culture. Repeat culture assures that treatment is effective. If a UTI is untreated, a child with vesicoureteal reflux of infected urine can develop renal scarring, which can cause renal hypertension and chronic renal failure. IV antibiotics assure adequate treatment so that complications (see benefits) are less likely to occur, but oral antibiotics allow for less invasive treatment (and decreased hospitalization) when that is acceptable. If sensitivities are not available to show that the antibiotic is appropriate, a repeat culture will show whether the antibiotic is working. If the child is being treated with an inappropriate antibiotic, one would want to correct the treatment immediately. Antibiotics must be taken long enough to ensure adequate treatment. Oral antibiotics are not considered adequate for pyelonephritis, which is more serious than simple UTI. Prophylaxis prevents future UTIs and therefore damage to kidneys and urologic system. 362

13 Radiologic Work-up 19. Any boy less than 10 years old with a first UTI or with systemic symptoms** (and/or who has not had the following study before) should have a VCUG and one of the following within three months of diagnosis: RUS, or IVP, or nuclear medicine renal scan. 20. Any girl less than 3 years old with a first UTI or less than 10 years old with systemic symptoms** (and/or who has not had the following studies before) should have a VCUG or IC and one of the following within three months of diagnosis: RUS, or IVP, or nuclear medicine renal scan. 21. If a child with a diagnosis of UTI remains febrile for more than 48 hours on therapy, or if repeat urine culture is positive despite appropriate antibiotics, the child needs an immediate evaluation for urologic obstruction or abscess with renal ultrasound (RUS), intravenous pyelogram (IVP), or nuclear medicine renal scan. 22. Children who have a VCUG or IC following a UTI should be on prophylactic or therapeutic antibiotics continuously from the beginning of therapy for the UTI until the time of the study. Vesicoureteral Reflux (VUR) 23. Children diagnosed with Grade II or higher VUR should be on prophylactic antibiotics until the reflux has resolved. Andrich and Majd, 1992; Gillenwater, 1991; Roth and Gonzalez in Oski et al., 1994; Sherbotie and Cornfeld, 1991; Andrich and Majd, 1992; Gillenwater, 1991; Roth and Gonzalez in Oski et al., 1994; Sherbotie and Cornfeld, 1991; Lebel in Oski et al., 1994 ; Lebel in Oski et al., 1994; Gillenwater, 1991; Andrich and Majd, 1992 Prevent damage to the urologic system. UTIs are rare in boys and are often associated with anatomic abnormalities. Uncomplicated UTIs are not uncommon in older girls, so a radiologic work-up is not typicallly necessary. Even with appropriate antibiotics, a UTI will often not resolve if there is an abscess or obstruction. Antibiotic treatment prevents reflux of infected urine. Reflux of infected urine is more likely to cause scarring than reflux of uninfected urine. Antibiotic treatment prevents reflux of infected urine. Reflux of infected urine is more likely to cause scarring than reflux of uninfected urine. 363

14 24. Children with VUR should have annual monitoring with VCUG or nuclear cystogram. 25. Children with high grade (Grade IV or higher) VUR or other anatomic abnormalities, such as posterior urethral valves, abnormal urethral implantation, or horse-shoe kidney, should be referred to a urologist. ; Gillenwater, 1991 Prevent allergic reaction to antibiotics. Decrease antibiotic resistance. Prevent allergic reaction to antibiotics. Decrease antibiotic resistance. The goal of annual monitoring is to detect early damage to kidneys as well as resolution of reflux. Determination of need for continued prophylaxis can be made based on monitoring test results. The references do not specify which grades count as "high grade," but common practice would count at least Grade as high grade. Some clinicians would refer for Grade II. 26. Children with obstructive symptoms should be referred to a urologist. 27. Children with VUR or other anatomic abnormalities who also have hypertension, decreased renal function, failure to thrive, or other related signs, should be referred to a pediatric nephrologist for treatment of renal insufficiency and hypertension. Prevent damage to the urologic system. Clinicians who do not believe in surgical management of reflux may not consider it necessary to refer to a urologist. However, urologists have the best training and experience to determine whether surgical or medical treatment is most appropriate. Specialist evaluation is important to ensure proper course of treatment. Prevent renal failure. Staff recommended this indicator. *Indicators for laboratory tests in the presence of fever in children under 36 months of age can be found in Chapter 12. Quality of Evidence Codes: I: RCT II-1: Nonrandomized controlled trials II-2: Cohort or case analysis II-3: Multiple time series : Opinions or descriptive studies 364

15 REFERENCES - URINARY TRACT INFECTION Andrich MP, and M Majd. September Diagnostic imaging in the evaluation of the first urinary tract infection in infants and young children. Pediatrics 90 (3): Gillenwater JY. March The role of the urologist in urinary tract infection. Medical Clinics of North America 75 (2): Kemper KJ, and ED Avner. March The case against screening urinalyses for asymptomatic bacteriuria in children. American Journal of Diseases of Children 146: Lebel MH Urinary tract infections. In Principles and Practice of Pediatrics, Second ed. Editors Oski FA, CD DeAngelis, RD Feigin, et al., Philadelphia, PA: J.B. Lippincott Company. Marks MI, and AC Arrieta Cystitis. In Textbook of Pediatric Infectious Diseases, Third ed. Editors Feigin RD, and JD Cherry, Philadelphia, PA: W.B. Saunders Company. Marks MI, and AC Arrieta Pyelonephritis. In Textbook of Pediatric Infectious Diseases, Third ed. Editors Feigin RD, and JD Cherry, Philadelphia, PA: W.B. Saunders Company. O'Donnell B The case for surgery. British Medical Journal 300: Roth DR, and ET Gonzales Urinary tract infection. In Principles and Practice of Pediatrics, Second ed. Editors Oski FA, CD DeAngelis, RD Feigin, et al., Philadelphia, PA: J.B. Lippincott Company. Sherbotie JR, and D Cornfeld. March Management of urinary tract infections in children. Medical Clinics of North America 75 (2): Stull TL, and JJ LiPuma. March Epidemiology and natural history of urniary tract infections in children. Medical Clinics of North America 75 (2): Treves ST. October The ongoing challenge of diagnosis and treatment of urinary tract infection, vesicoureteral reflux and renal damage in children. The Journal of Nuclear Medicine 35 (10): White RHR Management of urinary tract infection and vesicoureteric reflux in children: Operative treatment has no advantage over medical management. British Medical Journal 300:

16 Woodhead JC.. Genitourinary problems. In Ambulatory Pediatric Care, Second ed. Editor Dershewitz RA, Philadelphia, PA: J.B. Lippincott Company. Zelikovic I, RD Adelman, and PA Nancarrow. November Urinary tract infections in children: An update. Western Journal of Medicine 157 (5):