Predictors of Antimicrobial Resistance among Pathogens Causing Urinary Tract Infection in Children.

2016

116-21

2016 Apr

1097-6833

OBJECTIVE: To determine which children with urinary tract infection are likely to have pathogens resistant to narrow-spectrum antimicrobials.

STUDY DESIGN: Children, 2-71 months of age (n = 769) enrolled in the Randomized Intervention for Children with Vesicoureteral Reflux or Careful Urinary Tract Infection Evaluation studies were included. We used logistic regression models to test the associations between demographic and clinical characteristics and resistance to narrow-spectrum antimicrobials.

RESULTS: Of the included patients, 91% were female and 76% had vesicoureteral reflux. The risk of resistance to narrow-spectrum antibiotics in uncircumcised males was approximately 3 times that of females (OR 3.1; 95% CI 1.4-6.7); in children with bladder bowel dysfunction, the risk was 2 times that of children with normal function (OR 2.2; 95% CI 1.2-4.1). Children who had received 1 course of antibiotics during the past 6 months also had higher odds of harboring resistant organisms (OR 1.6; 95% CI 1.1-2.3). Hispanic children had higher odds of harboring pathogens resistant to some narrow-spectrum antimicrobials.

CONCLUSIONS: Uncircumcised males, Hispanic children, children with bladder bowel dysfunction, and children who received 1 course of antibiotics in the past 6 months were more likely to have a urinary tract infection caused by pathogens resistant to 1 or more narrow-spectrum antimicrobials.

10.1016/j.jpeds.2015.12.044

J. Pediatr.

26794472

Early Antibiotic Treatment for Pediatric Febrile Urinary Tract Infection and Renal Scarring.

2016

848-54

2016 Sep

2168-6211

<p><strong>Importance: </strong>Existing data regarding the association between delayed initiation of antimicrobial therapy and the development of renal scarring are inconsistent.</p>

<p><strong>Objective: </strong>To determine whether delay in the initiation of antimicrobial therapy for febrile urinary tract infections (UTIs) is associated with the occurrence and severity of renal scarring.</p>

<p><strong>Design, Setting, and Participants: </strong>Retrospective cohort study that combined data from 2 previously conducted longitudinal studies (the Randomized Intervention for Children With Vesicoureteral Reflux trial and the Careful Urinary Tract Infection Evaluation Study ). Children younger than 6 years with a first or second UTI were followed up for 2 years.</p>

<p><strong>Exposure: </strong>Duration of the child's fever prior to initiation of antimicrobial therapy for the index UTI.</p>

<p><strong>Main Outcomes and Measures: </strong>New renal scarring defined as the presence of photopenia plus contour change on a late dimercaptosuccinic acid renal scan (obtained at study exit) that was not present on the baseline scan.</p>

<p><strong>Results: </strong>Of the 482 children included in the analysis, 434 were female (90%), 375 were white (78%), and 375 had vesicoureteral reflux (78%). The median age was 11 months. A total of 35 children (7.2%) developed new renal scarring. Delay in the initiation of antimicrobial therapy was associated with renal scarring; the median (25th, 75th percentiles) duration of fever prior to initiation of antibiotic therapy in those with and without renal scarring was 72 (30, 120) and 48 (24, 72) hours, respectively (P = .003). Older age (OR, 1.03; 95% CI, 1.01-1.05), Hispanic ethnicity (OR, 5.24; 95% CI, 2.15-12.77), recurrent urinary tract infections (OR, 0.97; 95% CI, 0.27-3.45), and bladder and bowel dysfunction (OR, 6.44; 95% CI, 2.89-14.38) were also associated with new renal scarring. Delay in the initiation of antimicrobial therapy remained significantly associated with renal scarring even after adjusting for these variables.</p>

<p><strong>Conclusions and Relevance: </strong>Delay in treatment of febrile UTIs and permanent renal scarring are associated. In febrile children, clinicians should not delay testing for UTI.</p>

10.1001/jamapediatrics.2016.1181

JAMA Pediatr

27455161

Predictors of Non-Escherichia coli Urinary Tract Infection.

2016

2016 Jul 18

1532-0987

<p>We aimed to determine which children are prone to non-Escherichia coli coli UTIs. We included 769 children with UTI. We found that circumcised males, Hispanic children, children without fever, and children with Grade 3-4 VUR were more likely to have a UTI caused by organisms other than E. coli. This information may guide clinicians in their choice of antimicrobial therapy.</p>

10.1097/INF.0000000000001301

Pediatr. Infect. Dis. J.

27434831

Utility of sedation for young children undergoing dimercaptosuccinic acid renal scans.

2016

2016 Jun 10

1432-1998

<p><strong>BACKGROUND: </strong>No studies have examined whether use of sedation during a Tc-99 m dimercaptosuccinic acid (DMSA) renal scan reduces patient discomfort.</p>

<p><strong>OBJECTIVE: </strong>To compare discomfort level during a DMSA scan to the discomfort level during other frequently performed uroradiologic tests, and to determine whether use of sedation during a DMSA scan modifies the level of discomfort.</p>

<p><strong>MATERIALS AND METHODS: </strong>We examined the discomfort level in 798 children enrolled in the Randomized Intervention for children with Vesicoureteral Reflux (RIVUR) and Careful Urinary Tract Infection Evaluation (CUTIE) studies by asking parents to rate their child's discomfort level with each procedure on a scale from 0 to 10. We compared discomfort during the DMSA scan and the DMSA image quality between centers in which sedation was used &gt;90% of the time (sedation centers), centers in which sedation was used &lt;10% of the time (non-sedation centers), and centers in which sedation was used on a case-by-case basis (selective centers).</p>

<p><strong>RESULTS: </strong>Mean discomfort level was highest for voiding cystourethrogram (6.4), followed by DMSA (4.0), followed by ultrasound (2.4; P&lt;0.0001). Mean discomfort level during the DMSA scan was significantly higher at non-sedation centers than at selective centers (P&lt;0.001). No difference was apparent in discomfort level during the DMSA scan between sedation centers and selective centers (P=0.12), or between the sedation centers and non-sedation centers (P=0.80). There were no differences in the proportion with uninterpretable DMSA scans according to sedation use.</p>

<p><strong>CONCLUSION: </strong>Selective use of sedation in children 12-36&nbsp;months of age can reduce the discomfort level experienced during a DMSA scan.</p>

10.1007/s00247-016-3649-0

Pediatr Radiol

27287454

Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial.

2016

54-61

2016 Jan 7

1555-905X

<p><strong>BACKGROUND AND OBJECTIVES: </strong>The main objectives of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial were to evaluate the role of antimicrobial prophylaxis in the prevention of recurrent urinary tract infection (UTI) and renal scarring in children with vesicoureteral reflux (VUR). We present a comprehensive evaluation of renal scarring outcomes in RIVUR trial participants.</p>

<p><strong>DESIGN, SETTING, PARTICIPANTS, &amp; MEASUREMENTS: </strong>This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2-71 months with grade 1-4 VUR diagnosed after a first or second febrile or symptomatic UTI. Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years. Renal scarring was evaluated by baseline and follow-up (99m)technetium dimercaptosuccinic acid (DMSA) renal scans that were reviewed independently by two blinded reference radiologists.</p>

<p><strong>RESULTS: </strong>At the end of the study, 58 (10%) of 599 children and 63 (5%) of 1197 renal units had renal scarring. New renal scarring did not differ between the prophylaxis and placebo groups (6% versus 7%, respectively). Children with renal scarring were significantly older (median age, 26 versus 11 months; P=0.01), had a second UTI before enrollment (odds ratio [OR], 2.85; 95% confidence interval [95% CI], 1.38 to 5.92), were more likely to be Hispanic (OR, 2.22; 95% CI, 1.13 to 4.34), and had higher grades of VUR (OR, 2.79; 95% CI, 1.56 to 5.0). The proportion of new scars in renal units with grade 4 VUR was significantly higher than in units with no VUR (OR, 24.2; 95% CI, 6.4 to 91.2).</p>

<p><strong>CONCLUSIONS: </strong>Significantly more renal scarring was seen in relatively older children and in those with a second episode of febrile or symptomatic UTI before randomization. Preexisting and new renal scars occurred significantly more in renal units with grade 4 VUR than in those with low-grade or no VUR. Antimicrobial prophylaxis did not decrease the risk of renal scarring.</p>

10.2215/CJN.05210515

Clin J Am Soc Nephrol

26555605

Recurrent Urinary Tract Infections in Children With Bladder and Bowel Dysfunction.

2016

1-7

2016 Jan

1098-4275

<p><strong>BACKGROUND: </strong>Little generalizable information is available on the outcomes of children diagnosed with bladder and bowel dysfunction (BBD) after a urinary tract infection (UTI). Our objectives were to describe the clinical characteristics of children with BBD and to examine the effects of BBD on patient outcomes in children with and without vesicoureteral reflux (VUR).</p>

<p><strong>METHODS: </strong>We combined data from 2 longitudinal studies (Randomized Intervention for Children With Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation) in which children &lt;6 years of age with a first or second UTI were followed for 2 years. We compared outcomes for children with and without BBD, children with and without VUR, and children with VUR randomly assigned to prophylaxis or placebo. The outcomes examined were incidence of recurrent UTIs, renal scarring, surgical intervention, resolution of VUR, and treatment failure.</p>

<p><strong>RESULTS: </strong>BBD was present at baseline in 54% of the 181 toilet-trained children included; 94% of children with BBD reported daytime wetting, withholding maneuvers, or constipation. In children not on antimicrobial prophylaxis, 51% of those with both BBD and VUR experienced recurrent UTIs, compared with 20% of those with VUR alone, 35% with BBD alone, and 32% with neither BBD nor VUR. BBD was not associated with any of the other outcomes investigated.</p>

<p><strong>CONCLUSIONS: </strong>Among toilet-trained children, those with both BBD and VUR are at higher risk of developing recurrent UTIs than children with isolated VUR or children with isolated BBD and, accordingly, exhibit the greatest benefit from antimicrobial prophylaxis.</p>

10.1542/peds.2015-2982

Pediatrics

26647376

Antimicrobial Resistance and Urinary Tract Infection Recurrence.

2016

2016 Mar 11

1098-4275

<p><strong>BACKGROUND: </strong>The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial found that recurrent urinary tract infections (rUTI) with resistant organisms were more common in the trimethoprim-sulfamethoxazole prophylaxis (TSP) arm. We describe factors associated with trimethoprim-sulfamethoxazole (TMP-SMX) resistance of rUTIs in RIVUR.</p>

<p><strong>METHODS: </strong>Children aged 2 to 71 months with first or second UTI (index UTI) and grade I to IV vesicoureteral reflux (VUR) were randomized to TSP or placebo and followed for 2 years. Factors associated with TMP-SMX-resistant rUTI were evaluated.</p>

<p><strong>RESULTS: </strong>Among 571 included children, 48% were &lt;12 months old, 43% had grade II VUR, and 38% had grade III VUR. Recurrent UTI occurred in 34 of 278 children receiving TSP versus 67 of 293 children receiving placebo. Among those with rUTI, 76% (26/34) of subjects receiving TSP had TMP-SMX-resistant organisms versus 28% (19/67) of subjects receiving placebo (P &lt; .001). The proportion of TMP-SMX-resistant rUTI decreased over time: in the TSP arm, 96% were resistant during the initial 6 months versus 38% resistant during the final 6 months; corresponding proportions for the placebo arm were 32% and 11%. Among children receiving TSP, 7 (13%) of 55 with TMP-SMX-resistant index UTI had rUTI, whereas 27 (12%) of 223 with TMP-SMX-susceptible index UTI had rUTI (adjusted hazard ratio 1.38, 95% confidence interval 0.54-3.56). Corresponding proportions in placebo arm were 17 (26%) of 65 and 50 (22%) of 228 (adjusted hazard ratio 1.33, 95% confidence interval 0.74-2.38).</p>

<p><strong>CONCLUSIONS: </strong>Although TMP-SMX resistance is more common among children treated with TSP versus placebo, resistance decreased over time. Among children treated with TSP, there was no significant difference in UTI recurrence between those with TMP-SMX-resistant index UTI versus TMP-SMX-susceptible UTI.</p>

10.1542/peds.2015-2490

Pediatrics

26969273

Development and impact of an intervention to boost recruitment in a multicenter pediatric randomized clinical trial.

2014

151-7

2014 Feb

1938-2707

<p><strong>OBJECTIVES: </strong>Our primary objective was to develop and evaluate an intervention to increase recruitment in a multicenter pediatric randomized clinical trial (RCT). Our secondary objective was to assess the impact beyond 120 days.</p>

<p><strong>METHODS: </strong>The study was conducted at 17 academic centers participating in a pediatric RCT. The intervention consisted of utilizing a recruitment assessment tool at a site visit or teleconference with key site personnel.</p>

<p><strong>RESULTS: </strong>We found a significant increase in the number of individuals enrolled for all 17 sites at 120 days postintervention (mean = 1.12 per site; median = 1 per site; 95% confidence interval = 1-2; P = .04). No significant differences were apparent beyond the first 120 days postintervention.</p>

<p><strong>CONCLUSIONS: </strong>Successful recruitment in RCTs is essential to the quality, generalizability, and cost-effectiveness of clinical research. Implementation of this recruitment intervention may effectively increase recruitment in RCTs. Beyond the first 120 days postintervention, repeated interventions may be required. What is new? Despite general and pediatric-specific challenges to recruitment in RCTs, a paucity of evidence exists on effective recruitment strategies or assessment tools to reliably enhance recruitment. We developed a recruitment intervention for use in RCTs that enables clinical researchers to enhance recruitment.</p>

10.1177/0009922813506961

Clin Pediatr (Phila)

24151147

Risk factors for recurrent urinary tract infection and renal scarring.

2015

e13-21

07/2015

1098-4275

<p><strong>OBJECTIVES: </strong>To identify risk factors for recurrent urinary tract infection (UTI) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis.</p>

<p><strong>METHODS: </strong>This 2-year, multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux (VUR) receiving placebo in the RIVUR (Randomized Intervention for Vesicoureteral Reflux) study and 195 children with no VUR observed in the CUTIE (Careful Urinary Tract Infection Evaluation) study. Primary exposure was presence of VUR; secondary exposures included bladder and bowel dysfunction (BBD), age, and race. Outcomes were recurrent febrile or symptomatic urinary tract infection (F/SUTI) and renal scarring.</p>

<p><strong>RESULTS: </strong>Children with VUR had higher 2-year rates of recurrent F/SUTI (Kaplan-Meier estimate 25.4% compared with 17.3% for VUR and no VUR, respectively). Other factors associated with recurrent F/SUTI included presence of BBD at baseline (adjusted hazard ratio: 2.07 [95% confidence interval (CI): 1.09-3.93]) and presence of renal scarring on the baseline (99m)Tc-labeled dimercaptosuccinic acid scan (adjusted hazard ratio: 2.88 [95% CI: 1.22-6.80]). Children with BBD and any degree of VUR had the highest risk of recurrent F/SUTI (56%). At the end of the 2-year follow-up period, 8 (5.6%) children in the no VUR group and 24 (10.2%) in the VUR group had renal scars, but the difference was not statistically significant (adjusted odds ratio: 2.05 [95% CI: 0.86-4.87]).</p>

<p><strong>CONCLUSIONS: </strong>VUR and BBD are risk factors for recurrent UTI, especially when they appear in combination. Strategies for preventing recurrent UTI include antimicrobial prophylaxis and treatment of BBD.</p>

10.1542/peds.2015-0409

Pediatrics

26055855