Massoud Majd

Oral Versus Initial Intravenous Therapy for Urinary Tract Infections in Young Febrile Children

Background. The standard recommendation for treatment of young, febrile children with urinary tract infection has been hospitalization for intravenous antimicrobials. The availability of potent, oral, third-generation cephalosporins as well as interest in cost containment and avoidance of nosocomial risks prompted evaluation of the safety and efficacy of outpatient therapy. Methods. In a multicenter, randomized clinical trial, we evaluated the efficacy of oral versus initial intravenous therapy in 306 children 1 to 24 months old with fever and urinary tract infection, in terms of short-term clinical outcomes (sterilization of the urine and defervescence) and long-term morbidity (incidence of reinfection and incidence and extent of renal scarring documented at 6 months by99mTc-dimercaptosuccinic acid renal scans). Children received either oral cefixime for 14 days (double dose on day 1) or initial intravenous cefotaxime for 3 days followed by oral cefixime for 11 days. Results. Treatment groups were comparable regarding demographic, clinical, and laboratory characteristics. Bacteremia was present in 3.4% of children treated orally and 5.3% of children treated intravenously. Of the short-term outcomes, 1) repeat urine cultures were sterile within 24 hours in all children, and 2) mean time to defervescence was 25 and 24 hours for children treated orally and intravenously, respectively. Of the long-term outcomes, 1) symptomatic reinfections occurred in 4.6% of children treated orally and 7.2% of children treated intravenously, 2) renal scarring at 6 months was noted in 9.8% children treated orally versus 7.2% of children treated intravenously, and 3) mean extent of scarring was ∼8% in both treatment groups. Mean costs were at least twofold higher for children treated intravenously (

Renal Scarring Following Reflux and Nonreflux Pyelonephritis in Children: Evaluation with 99mTechnetium-Dimercaptosuccinic Acid Scintigraphy

3577 vs

Dimercaptosuccinic Acid Renal Scintigraphy For The Evaluation of Pyelonephritis and Scarring: A Review of Experimental and Clinical Studies

1473) compared with those treated orally. Conclusions. Oral cefixime can be recommended as a safe and effective treatment for children with fever and urinary tract infection. Use of cefixime will result in substantial reductions of health care expenditures.

EVALUATION OF 99MTECHNETIUM-DIMERCAPTO-SUCCINIC ACID RENAL SCANS IN EXPERIMENTAL ACUTE PYELONEPHRITIS IN PIGLETS

99mTechnetium dimercaptosuccinic acid (DMSA) scintigraphy is the imaging modality of choice for the detection of acute pyelonephritis and chronic renal scarring in children. Using the DMSA scan we prospectively evaluated renal scarring after reflux and nonreflux pyelonephritis in children. The study population consisted of 33 patients with acute pyelonephritis documented by a DMSA renal scan at infection. The children were evaluated for renal scarring with a followup DMSA scan 4 to 42 months (mean 10.7 months) after the acute infection. All new scarring on followup DMSA scans occurred at sites corresponding exactly to areas of acute inflammation on the initial DMSA scan. Therefore, only those kidneys with acute changes on the initial scan were subsequently analyzed. Of 38 kidneys new or progressive scarring developed in 16 (42%), including 6 of 15 (40%) with associated vesicoureteral reflux and 10 of 23 (43%) without demonstrable reflux. New renal scarring developed in 6 of the 7 kidneys (86%) associated with a neuropathic bladder or posterior urethral valves. In contrast, new scarring developed in only 10 of 31 kidneys (32%) associated with a normal bladder (p = 0.028). Excluding the kidneys associated with a neuropathic bladder or posterior urethral valves, new renal scarring developed in 3 of 12 (25%) with primary reflux, compared with 7 of 19 (37%) without vesicoureteral reflux. Except for the white blood count and the species of infecting bacteria, no other statistically significant differences could be found between those cases in which scars did or did not develop. We conclude that acquired renal scarring only occurs at sites corresponding to previous areas of acute pyelonephritis, the acute parenchymal inflammatory changes of acute pyelonephritis are reversible and do not lead to new renal scarring in the majority of cases, and once acute pyelonephritis has occurred ultimate renal scarring is independent of the presence or absence of vesicoureteral reflux.

A Nonsurgical Approach to the Management of Primary Vesicoureteral Reflux

Renal cortical scintigraphy has been reported to be useful in children for confirmation of the diagnosis of acute pyelonephritis. Subsequent experimental studies have demonstrated that dimercaptosuccinic acid (DMSA) scintigraphy, when compared directly with histopathology, is highly reliable for the detection and localization of parenchymal inflammatory changes associated with acute pyelonephritis. Recent clinical studies of acute pyelonephritis using DMSA scintigraphy reveal that the majority (50 to 91%) of children with febrile urinary tract infections have abnormal DMSA renal scan findings and that the majority of these children do not have demonstrable vesicoureteral reflux. However, when vesicoureteral reflux is present, renal cortical abnormalities are demonstrated by DMSA scintigraphy in 79 to 86% of the kidneys. In children with febrile urinary tract infections routine clinical and laboratory parameters are not reliable in the differentiation of acute pyelonephritis, documented by DMSA renal scan findings, from urinary tract infections without parenchymal involvement. Furthermore, the presence of P-fimbriated Escherichia coli associated with febrile urinary tract infections does not reliably predict those kidneys that have acute parenchymal inflammation demonstrated by DMSA renal scans. DMSA is also the isotope agent of choice for the detection of renal scarring. Clinical studies report greater sensitivity of DMSA renal scintigraphy for the detection of renal scarring when compared with the excretory urogram, particularly in infants and young children. In a recent prospective study of post-pyelonephritic renal scarring in children we found that acquired renal scarring only occurs in sites corresponding exactly to previous areas of acute pyelonephritis demonstrated by DMSA scintigraphy at the time of infection. Furthermore, once acute pyelonephritis occurs, ultimate renal scarring is independent of the presence or absence of vesicoureteral reflux. These findings provide convincing evidence that renal parenchymal infection, rather than vesicoureteral reflux, is the prerequisite for acquired (postnatal) renal scarring. Vesicoureteral reflux as a risk factor for acquired renal scarring is directly related to its role as a risk factor for acute pyelonephritis. We conclude that DMSA scintigraphy is a valid tool for confirming the diagnosis of acute pyelonephritis in children and for identifying kidneys at risk for subsequent renal scarring.

Comparison of the diuretic renogram and the pressure perfusion study in children.

We evaluated the sensitivity and specificity of 99mtechnetium-dimercapto-succinic acid renal scans in the detection and localization of experimental acute pyelonephritis in piglets. To create pyelonephritis vesicoureteral reflux of infected urine was surgically induced in 22 piglets. Nine animals were evaluated with a dimercapto-succinic acid renal scan at 1 week and 13 at 2 weeks. Autopsy and histopathological examination of the kidneys were performed subsequently. The location and extent of the inflammatory response found on histopathological examination were compared to dimercapto-succinic acid renal scan findings in a blinded fashion. Of the 22 kidneys subjected to vesicoureteral reflux 15 had positive histopathological findings of acute pyelonephritis, including 13 detected by the dimercapto-succinic acid renal scan findings. The 2 kidneys in which inflammation was not detected had only minimal grade I lesions and were grossly normal. There were no false positive scans in any of these kidneys. The sensitivity of the scan for detection of acute pyelonephritis in the kidneys subjected to reflux was 87 per cent and the specificity was 100 per cent. Furthermore, in these same kidneys the dimercapto-succinic acid renal scan findings correctly predicted the presence or absence of individual pyelonephritic lesions in 62 of 66 poles for an over-all agreement rate of 94 per cent. Thus, dimercapto-succinic acid renal cortical imaging is a highly sensitive and reliable imaging modality to detect and localize experimental acute pyelonephritis in piglets.

Pyelonephritis in Male Infants: How Important is the Foreskin?

We performed a retrospective review to evaluate the results of a nonsurgical approach to the management of primary vesicoureteral reflux during a 10-year period (1976 to 1986). During that interval patients with reflux were studied initially with a standard voiding cystourethrogram and either an excretory urogram or a renal scan with glomerular filtration rate and/or differential renal function determination. Height, weight, blood pressure, urine cultures and serum creatinine measurements also were obtained. Isotope cystography was used for followup examinations. A single, negative isotope cystogram was the radiological criterion for cessation of reflux. The charts of 545 children (55 per cent had bilateral reflux) with 844 refluxing ureters were reviewed. Based upon the international classification vesicoureteral reflux was grade I in 6.6 per cent of the cases, grade II in 54.2 per cent, grade III in 31.6 per cent, grade IV in 5.7 per cent and grade V in 1.9 per cent. All children were kept on long-term continuous prophylactic antibiotics and they were re-evaluated annually with isotope cystography. The followup rate for the entire group was 88 per cent. During the observation period spontaneous resolution of reflux was noted in 36 per cent of the patients and 39 per cent of the total refluxing ureters. Only 13 per cent of the entire group underwent surgical correction of reflux. Presently, 39 per cent (215) of the patients continue to be followed with reflux. Of the total group 66 patients (12 per cent) were lost to followup. In the 194 patients with spontaneous resolution of reflux the mean duration of reflux was 1.69 years, with 30 to 35 per cent resolving each year. Based on Students t test there was a significant difference in duration of reflux in patients with grade II compared to grade III reflux (1.56 versus 1.97 years, p less than 0.04). When age at presentation was compared with duration of reflux there was a significantly shorter duration of reflux only in those patients presenting from age 0 to 12 months, compared to those 13 months and older (1.44 versus 1.85 years, p less than 0.02). Renal function was evaluated by serum creatinine, calculated glomerular filtration rate or differential diethylenetriaminepentaacetic acid scan results.(ABSTRACT TRUNCATED AT 400 WORDS)

Renal scarring and vesicoureteral reflux in children with myelodysplasia

We evaluated 42 hydronephrotic kidneys with diuretic renography and pressure perfusion studies to diagnose or exclude the presence of obstruction. Both studies were highly accurate but a small number of false positive and false negative studies were observed with each testing modality. The advantages, disadvantages and potential sources of inaccuracy of each study are discussed, and a protocol for the evaluation of hydronephrosis incorporating both studies is proposed.

Feeding disorders and gastroesophageal reflux in infants with chronic renal failure

We investigated the association of the uncircumcised foreskin and pyelonephritis in male infants less than 6 months old. During a 21-month prospective study 94 children (age range 2 weeks to 18.9 years) were hospitalized for febrile urinary tract infection. The male-to-female ratio for 35 patients less than 6 months old was 2.2:1. Of 59 patients older than 6 months the male-to-female ratio was reversed at 0.25:1 (p less than 0.001). In 13 of 24 infants (54%) less than 6 months old and in 8 of 12 boys (67%) older than 6 months a dimercaptosuccinic acid renal scan documented acute parenchymal damage (p = 0.72). Vesicoureteral reflux or other genitourinary abnormalities were found in only 3 of 24 patients (12.5%) less than 6 months old compared with 6 of 12 boys (50%) older than 6 months (p = 0.036). Of 24 infants less than 6 months old 22 (92%) were uncircumcised compared with 6 of 12 boys (50%) older than 6 months (p = 0.009). We then retrospectively compared the circumcision status of the infants who had febrile urinary tract infection with a control group of 63 infants matched for age, race and socioeconomic status hospitalized with febrile upper respiratory infection during a similar period. The frequency of uncircumcised infants in the control group with febrile upper respiratory infection was only 44% (28 of 63) compared with 91% of infants with febrile urinary tract infection (p less than 0.001). Overall the findings of the male predominance among patients less than 6 months old with febrile urinary tract infection, the disproportionately high frequency of infants with febrile urinary tract infection who were not circumcised, and the disproportionately low occurrence of vesicoureteral reflux and other genitourinary abnormalities in infants with febrile urinary tract infection strongly support an association between circumcision status and the risk for febrile urinary tract infection and pyelonephritis in male infants.

Effect of phenobarbital on 99mTc-IDA scintigraphy in the evaluation of neonatal jaundice

The records of 180 myelodysplasia patients followed from 3 to 18 years were reviewed. Studies included cystography to evaluate vesicoureteral reflux and dimercapto-succinic acid renal scintigraphy to identify acute inflammation and renal scarring. Scarring was noted in 28 of 180 patients (15.5%), of whom 68% were girls. Of the patients with renal scarring 75% had associated reflux and 40% over-all were identified as having reflux. Management of patients with vesicoureteral reflux included clean intermittent catheterization, antibiotic prophylaxis and anticholinergics when indicated. Only 17 of 72 patients (24%) had ureteral reimplantation. Surgical indications included persistent high grade reflux and/or progressive upper tract damage. Reflux resolved in 62% of those on medical management. Resolution was not dependent on grade of reflux (as compared to primary reflux). Twenty-one patients are stable and being followed with persistent reflux. In 7 patients new renal scars developed during aggressive medical management, 5 of whom underwent subsequent surgical correction.