Urinary Tract Infections

Hormonal Therapy continued that healthy postmenopausal women should not use estrogen/progestin to prevent chronic disease. What does this study mean to urologists? Unfortunately, no urological issues were assessed in the study. We think it is logical to extrapolate from the study results that estrogen/progestin must be considered unproven for the If hormone therapy is used for urological symptoms, the potential for harm may be greater than the unproven, perceived benefit. prevention or therapy of urological conditions such as urge or stress incontinence, overactive bladder, or UTIs unless these claims can be supported by well-designed and executed scientific studies. Moreover, if hormone therapy is used for urological symptoms, the potential for harm may be greater than the unproven, perceived benefit. Menopausal Hormone Replacement Therapy and Risk of Ovarian Cancer Lacey JV, Jr, Mink PJ, Lubin JH, et al. JAMA. 2002;288:334–341. In the same issue of JAMA, Lacey and colleagues reported the results of their follow-up study of a 1979-1998 cohort of women who were recruited to participate in the Breast Cancer Detection Demonstration Project, a nationwide breast-cancer screening program conducted at 29 U.S. centers. The objective of this study was to determine whether HRT using estrogen only, estrogen/progestin only, or estrogen only followed by estrogen/progestin increases the risk of ovarian cancer. More than 44,000 postmenopausal women (mean age at start of follow-up, 56.6 years) participated in the study. In 1979, the National Cancer Institute added questions concerning ovarian cancer and its suspected risk factors (including HRT) to the follow-up questionnaires. The analyses of these data by Lacey and colleagues show that women who used estrogen-only HRT had a significantly increased risk of later development of ovarian cancer. Everyone knows that elderly women frequently develop severe osteoporosis, resulting in a life complicated by constant back pain and repeated fractures. By the 1970s, it had become clear that the use of estrogenic substances at or near the time of menopause could prevent or treat osteoporosis, and these drugs became widely prescribed and taken for this purpose. Even before the bone-sparing effects of estrogen were known, these agents had been used extensively for the treatment of menopausal symptoms, primarily vasomotor 132 VOL. 5 NO. 2 2003 REVIEWS IN UROLOGY instability and vaginal atrophy. Estrogens were also thought to prevent coronary artery disease and to delay the onset of Alzheimer’s disease. It is not surprising that the pharmaceutical industry developed numerous estrogenic agents that could be swallowed, placed in the vagina, applied with a patch, or rubbed into the skin, and that these agents have been prescribed for and are now used by millions of women. However, recent secondary prevention studies provide compelling evidence that there is no protection against further cardiovascular events for women with coronary heart disease who take these agents, and there may be real harm. Lacey and colleagues identified 329 women who developed ovarian cancer during the follow-up. When adjusted for age, type of menopause, and use of oral contraceptives, the results showed that the use of estrogen only was significantly associated with ovarian cancer. The study concluded that women who used estrogen-only replacement therapy, particularly for 10 or more years, were at significantly increased risk of ovarian cancer. Women who used short-term estrogen/progestin–only replacement therapy were not at increased risk. Doctors who counsel women about HRT must consider the unique needs of each patient and attempt to weigh the benefits and risks of therapy on an individual basis. Currently, certain benefits such as prevention of osteoporosis and treatment of vasomotor symptoms are acknowledged. Any postmenopausal women who have not had a hysterectomy, however, should not receive estrogen only, as there is an unquestionable increased risk of endometrial, breast, and ovarian cancer. Urinary Tract Infections Management of Urinary Tract Infections in Children: Simplifying the Controversies? Reviewed by J. Curtis Nickel, MD Department of Urology, Queen’s University, Kingston, Ontario, Canada [Rev Urol. 2003;5(2):132-134] T he management of urinary tract infections (UTIs) in children has confused urologists for decades. The controversy regarding whom to investigate, how to Urinary Tract Infections investigate, and how to treat has embroiled pediatric urologists in what seems to be an endless debate. The general urologist, who also covers pediatric urology, is left out of the loop and has to make decisions about these questions on a daily basis. Guidelines from the American Academy of Pediatrics recommend obtaining a voiding cystourethrogram and a renal ultrasonogram for young children after the first UTI; however, many practicing urologists do not consistently perform these tests or use other methods to determine the integrity of the urinary tract. This is because many feel that the results of the tests do not influence the management plan they adopt. Similarly, once the UTI has occurred, the optimal duration of oral antibiotic therapy for UTI in children has never been determined to every urologist’s satisfaction. Imaging Studies After a First Febrile Urinary Tract Infection in Young Children Hoberman A, Charron M, Hickey RW, et al. N Eng J Med. 2003;348:251-252. Hoberman and colleagues investigated whether imaging studies altered management or improved outcomes in young children with a first febrile UTI. The investigators prospectively obtained an ultrasonogram and an initial renal scan within 72 hours in 309 children, 1-24 months old, who had a first documented UTI and a fever of 38.3°C or greater. One month later, a contrast voiding cystourethrogram was performed, and 6 months later, renal scanning was repeated. Initial renal ultrasonography was abnormal in only 12% of the children, and none of the identified abnormalities influenced the management of the children’s UTIs. Voiding cystourethrography, performed in 302 of the children, showed vesicoureteral reflux in 39%. The reflux was low grade (grade I, II, or III) in 96% of these children. Renal scarring was noted in 9.5% of these children (26 in total) on repeated scans. The renal ultrasonogram in this study was a poor predictor of vesicoureteral reflux. Commentary Urologists perform diagnostic imaging of the kidneys and urinary tract in children with their first febrile UTI on the assumption that early detection of urologic abnormalities will lead to changes in management and improved outcomes. Hoberman and colleagues point out that there is little evidence that this practice results in prevention of renal scarring, hypertension, or renal failure. There have really been no controlled trials or analyses that evaluate the effect of imaging studies on management, whereas there have been studies to evaluate the prevalence of urologic abnormalities in children and the sensitivity and specificity of various imaging techniques. We do not know the value of these findings in improving outcomes. This study did confirm that ultrasonography is not sensitive enough to consistently detect vesicoureteral reflux. In 309 children in this particular study, ultrasonographic results also failed to identify obstruction of the urinary tract with This study further confirmed that ultrasonography is not sensitive enough to consistently detect vesicoureteral reflux. any expected accuracy. The authors therefore did not recommend routine performance of renal ultrasonography after the diagnosis of a first febrile UTI in children who have undergone a prenatal ultrasound after 30–32 weeks of gestation (fetal ultrasonography frequently identifies children with obstructive lesions of the urinary tract in utero). The urologic practice of initiating long-term prophylactic antimicrobial therapy in children found to have vesicoureteral reflux (really an empirical approach) has recently been questioned. The theory that continuous prophylactic antimicrobial therapy successfully prevents infection until reflux resolves spontaneously or is corrected surgically, and that this practice will prevent scarring, has recently been questioned by many pediatric urologists. If it is certain (and we would need a placebo-controlled study) that continuous prophylactic antimicrobial therapy prevents renal scarring in children with vesicoureteral reflux, only then would it be necessary and important to perform a voiding cystourethrogram. The results of this very large study suggest that renal ultrasonography and renal scanning at the time of acute illness are of limited value because they do not provide information that modifies management. The use of voiding cystourethrography to identify children with vesicoureteral reflux continues to be recommended, under the so-far unproved assumption that continuous prophylactic antimicrobial therapy is effective in reducing the incidence of reinfection and renal scarring. This reviewer believes that renal ultrasonography is a safe and cost-effective means of assessing the anatomic features of the upper urinary tract and should continue to be used when a clinical situation demands this information. Furthermore, the data continue to support the performance of a voiding cystourethrogram after a first febrile UTI in children less than 24 months of age and perhaps in some patients older than 24 months of age. Pediatric urologists need to convince the rest of us that these imaging VOL. 5 NO. 2 2003 REVIEWS IN UROLOGY 133 Urinary Tract Infections continued studies change management and that contemporary management of employing prophylactic antibiotics in these children actually prevents adverse future outcomes. Short Versus Standard Duration Oral Antibiotic Therapy for Acute Urinary Tract Infection in Children (Cochrane Review) UTI in children directly after treatment and 1–15 months after treatment. There was also no significant difference between short- and standard-duration therapy in the development of resistant organisms at the end of therapy or in incidence of posttreatment recurrent UTIs. The Cochrane reviewers concluded that a 2–4-day course of oral antibiotics appears to be as effective as a 7–14 day course in eradicating lower UTI in children. Michael M, Hodson EM, Craig, JC, et al. Cochrane Database Syst Rev. 2002;(1):CD003966. Although urologists have generally accepted that 3-day antibiotic therapy for acute simple cystitis in adults is superior to single-dose and equivalent to 7-day therapy, the optimal duration of oral antibiotic therapy for UTI in children has not been determined. Studies have compared single-dose therapy to standard 7–10 day therapy for UTI with mixed results, and most urologists, pediatric or gen- The authors concluded that a 2–4-day course of oral antibiotics appears to be as effective as a 7–14-day course in eradicating lower urinary tract UTI in children. eral, do not advocate single-dose therapy. In this review, Michael and colleagues assessed the benefits and harms of short-course (2–4 days) compared with standard-duration (7–14 days) oral antibiotic treatment for acute UTI in children. The authors identified 10 randomized and quasirandomized controlled trials comparing short-term with standard oral antibiotic therapy in children aged 3 months to 18 years with culture-proven UTI. In these 10 trials, 652 children were evaluated. There was no significant difference in the frequency of positive urine cultures between the short- (2–4 days) and standard-duration oral antibiotic therapy (7–14 days) for 134 VOL. 5 NO. 2 2003 REVIEWS IN UROLOGY Commentary This systemic review provides solid evidence for urologists to treat children with only a short course of antibiotics (cost-effective and safer). The review does not address the controversy that arises from a review of the article by Hoberman and colleagues, questioning the value of antimicrobial prophylaxis in preventing long-term adverse outcomes in children with and without abnormalities detected on initial imaging studies. This reviewer intends to do the following: 1) to continue to obtain renal ultrasonography in young children (younger than 24 months) who present with a febrile UTI who do not have a normal prenatal ultrasound and in selected older children who do not respond to antibiotic therapy or have an abnormal history (ie, calculus) or physical examination (ie, palpable abdominal mass); 2) to continue to perform a voiding cystourethrogram in young children (younger than 24 months) with a first febrile UTI and in selected older children with either a first, refractory, or recurrent febrile UTI; and 3) to treat single episodes of UTIs, particularly lower UTIs not associated with fever, with 2–4 days of antibiotics and continue to consider longer courses of antibiotics for patients with febrile UTIs (ie, pyelonephritis) and lower urinary tract abnormalities. This reviewer will continue to follow this approach until such time as pediatric urologists have undertaken the studies that confirm or refute the value of this practice.