Breakthrough Urinary Tract Infection Research Articles

Pattern of urinary tract infection in children with vesicoureteric reflux: Does breastfeeding reduce the occurrence of urinary tract infection?

The protective factors against urinary tract infections (UTIs) in the setting of vesicoureteric reflux (VUR) remain poorly defined. Breastfeeding was suggested as a protective factor against UTI, but its role remains undetermined in this highly susceptible population. The objective of the study was to identify the pattern and risk factors of UTI and investigate the effect of breastfeeding on UTI occurrence in VUR children. This was a mixed-method design, whereby the first part was a cross-sectional study that included children who were diagnosed with VUR and were assessed for their UTI pattern. The second part was a case-control study, which involved contacting the mothers of the children enrolled and questioning them about their breastfeeding pattern, and UTI development was assessed. Our study included 62 children with a median age of 4.4 (interquartile range = 21) months at diagnosis. Of those, 37 (60%) were male and 25 (40%) were female. Most UTIs occurred in the first 3 months of life, and the first episodes were more frequent in males. Constipation was significantly associated with the occurrence of UTI (relative risk [RR] =1.750 [95% confidence interval (CI): 1.231-2.489], P = 0.003). Children with breakthrough UTIs were more likely to have been breastfed for <9 months (odds ratio [OR] = 4.091 [95% CI: 1.287-13.002], P = 0.015) and to have been exclusively breastfed for <2 months (OR = 4.600 [95% CI: 1.337-15.823], P = 0.012). Children with VUR are more susceptible to UTIs in their 1st year of life. Constipation is a major risk factor for UTI occurrence in VUR children and should be aggressively managed. Breastfeeding for longer durations showed promising protective features against breakthrough UTIs.

Risk factors for new renal scarring in children with vesicoureteral reflux receiving continuous antibiotic prophylaxis

To investigate the risk factors for new renal scarring (NRS) in children with vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP). This was a single-center cohort study. The clinical data of 140 children with grade I–V VUR receiving CAP were analyzed. In this study, exposure variables were sex, younger age at the initial diagnosis of UTI ≤ 12 months, the occurrence of breakthrough urinary tract infection (BT-UTI), high-grade VUR, bilateral VUR, etiology, presence of renal scarring at the initial diagnosis and ultrasound abnormalities. The outcome was NRS. A total of 140 children were included in the risk factor analysis of NRS, 73 of whom experienced NRS, an incidence rate of 52.14%. Multivariate Cox regression suggested that the presence of renal function impairment after the initial diagnosis of UTI (OR 3.411, 95% CI 1.5751–6.646) and the occurrence of BT-UTI while receiving CAP (OR 1.995, 95% CI 1.089–2.958) were independent risk factors for NRS. Multivariate Cox regression showed that high-grade VUR had no significant effects on NRS (OR 0.940, 95% CI 0.462–1.912, P = 0.864). No significant difference was identified in multivariate Cox regression analysis in the IV–V group (vs I–III group) (OR 0.960, 95% CI 0.565–1.633, P = 0.960). Renal function impairment after the initial diagnosis of UTI and the occurrence of BT-UTI while receiving CAP were independent risk factors for NRS. Neither univariate analysis nor multivariate analysis found a correlation between VUR grade and NRS.

Primary repair vs Delayed staged repair in infants with primary obstructive megaureters and their long term outcomes – A single centre experience

There is paucity of literature in the management of infants with primary obstructive megaureters undergoing upfront primary repair with an extravesical technique of ureteral re implantation (with or without ureteral tailoring). To compare 2 different approaches in the management of infants with unilateral primary obstructive megaureters. This was a retrospective analysis of a prospectively maintained data base between 2005 and 2021. Infants <1 year with unilateral primary obstructive megaureter were included. They were divided into 2 groups: those who underwent an upfront extravesical ureteric reimplantation with or without ureteral tailoring during infancy -Primary Repair (PR), and those who initially underwent a low end cutaneous ureterostomy during infancy followed by take down of ureterostomy and intravesical ureteric reimplantation after 1 year of age -Delayed staged repair (DSR). Children presenting with sepsis, in whom a diversion was imperative, were excluded. All children were followed up annually after their definitive repair with a renal ultrasound, diuretic renogram, estimated glomerular filtration rate and assessment of voiding dysfunction if present. The 1st year and 3rd year follow up details were collated and analysed. Failure was defined as persistent obstructive pattern on renogram with worsening differential renal function or presence of high grade reflux with recurrent breakthrough urinary tract infection; both of which necessitated a redo reimplantation following the definitive surgery. There were 18 infants in Primary repair and 16 infants in Delayed Staged Repair. Urinary tract infections was the commonest presenting symptom amongst both groups i.e. > 50%.The post operative complication rate was 11% in Primary repair and 31% in Delayed Staged Repair. One child in each of the groups (2 girls) required redo reimplantation (5.8%). At the end of the 3rd year follow up (from the definitive repair) there was significant reduction in the hydronephrosis, improvement in the differential renal function with no evidence of obstruction and improvement in the estimated glomerular filtration rate amongst all in both groups which was statistically significant i.e. p<0.05. The success rate was 94.4% in Primary Repair and 93.75% in Delayed Staged Repair. The mean follow up was 9.7 years amongst those undergone Primary Repair and 9 years amongst those undergone Delayed Staged Repair. Primary extravesical ureteral reimplantation may be considered as the preferred line of management of unilateral obstructed megaureters during infancy.

Antimicrobial resistance of breakthrough urinary tract infections in young children receiving continual antibiotic prophylaxis.

Continual antibiotic prophylaxis (CAP) can reduce the risk of recurrent UTI (rUTI). However, antimicrobial resistance in subsequent UTIs is a concern. This study aimed to explore antimicrobial resistance in young children prescribed CAP for rUTIs. A retrospective review of patient records/microbiology results was undertaken for children < 2years of age, on CAP, with 2-3 clean catch/mid-stream/supra-pubic aspirate urine cultures with a pure growth of bacteria, between January 2017 and December 2019. One hundred twenty-four urine specimens from 54 patients (26 (48%) males, median age 6months) were analysed. CAP prescribed was trimethoprim in 37 (69%), cefalexin in 11 (29%), and nitrofurantoin in 6 (11%). Based on antimicrobial susceptibility of the index UTI within the study period, 41 patients (76%) grew organisms on urine culture classified as sensitive and 13 (24%) resistant. Thirty-five (65%) children had congenital anomaly of the kidneys and urinary tract (CAKUT); they were more likely to be in the resistant group (P = 0.032). Escherichia coli (37/54, 69%) was the commonest index uropathogen. The resistant group had a higher proportion of non-E. coli index UTI pathogens (P = 0.098). Breakthrough UTI with a CAP-resistant organism was more likely in the resistant group (P = 0.010). Age, sex, and kidney scarring on DMSA (dimercaptosuccinic acid) scan were not significantly different between groups. Conclusion: Over a 3-year period, the proportion of children on CAP with resistant organism UTI doubled and resistant infections were more likely in children with CAKUT. Development of non-antimicrobial prophylaxis options is required. What is Known: • Recurrent urinary tract infections are common in children, particularly in those with underlying anatomical abnormalities of the kidneys and urinary tract. •Continuous antibiotic prophylaxis is used frequently in these children, however there is a lack of consensus on whether the potential benefits of CAP outweigh the harms. What is New: • This study adds further evidence towards the consequences of using continuous antibiotic prophylaxis in recurrent UTI; specifically, a 2-fold increase in antimicrobial resistance was seen in subsequent UTIs following long-term use of CAP, providing further vigour for the need for non-antibiotic alternatives.

V04-05 ROBOT-ASSISTED LAPAROSCOPIC EXTRAVESICAL BILATERAL URETERAL REIMPLANTATION: LUAA TECHNIQUE

You have accessJournal of UrologyCME1 Apr 2023V04-05 ROBOT-ASSISTED LAPAROSCOPIC EXTRAVESICAL BILATERAL URETERAL REIMPLANTATION: LUAA TECHNIQUE Parviz Hajiyev, Jared Fialkoff, and Mohan Gundeti Parviz HajiyevParviz Hajiyev More articles by this author , Jared FialkoffJared Fialkoff More articles by this author , and Mohan GundetiMohan Gundeti More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003252.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In today's era of minimally invasive surgery, robotic-assisted laparoscopic ureteral reimplantation (RALUR) is being popularly performed at many centers. We previously described the LUAA technique (Eur Urol 2016; 70(5):818–823). METHODS: Through this video, we share the step-by-step technical details of the “LUAA” (L-length of ureteric tunnel, U- the u stitch at UVJ, A- placement of the ureteral apical alignment suture and A- ensuring inclusion of adequate ureteral adventitia in detrusorrhaphy) for bilateral ureteric reimplantation. A 4 years old girl presented with recurrent urinary tract infections (UTI) . Her voiding cystourethrogram (VCUG) was suggestive of bilateral high grade of vesicoureteric reflux (VUR), and DMSA scan showed multiple scars. RESULTS: For this persistent bilateral VUR with breakthrough UTIs beyond the age of toilet training, she underwent a robotic-assisted laparoscopic ureteric reimplantation- bilateral (RALUR-b) by the “LUAA” technique. CONCLUSIONS: Postoperative she had USS one month and one year and was normal. The VCUG at 4 months showed resolved VUR bilateral. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e339 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Parviz Hajiyev More articles by this author Jared Fialkoff More articles by this author Mohan Gundeti More articles by this author Expand All Advertisement PDF downloadLoading ...

Intravesical gentamicin treatment for recurrent urinary tract infections: A systematic review over the last two decades

Objectives: Recurrent urinary tract infections (rUTIs) have a significant effect on a patient’s quality of life and frequent use of antibiotics increases multi-drug resistance. Previous research on intravesical antibiotics suggests that this has a local effect on bacteria with reduced systemic absorption and associated side effects. We conducted a systematic review to assess the effectiveness and adverse effects of intravesical gentamicin treatment. Methods: Systematic review of all English published articles from January 2001 to October 2021 according to the Cochrane and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards. Results: A total of 139 studies were identified, 20 full-text articles were screened and 6 subsequently included totalling 166 patients. All studies reported a decrease in the mean number of urinary tract infections (UTIs) with a significant reduction ( p = 0.0025 and p &lt; 0.004) in two studies. When the number of breakthrough UTIs on prophylactic gentamicin installations was assessed, 65% ( n = 86/133) remained UTI free. Throughout treatment, 99% of serum gentamicin levels were &lt;0.3 ng/dL, and reported instances of increased creatinine were low (2%). A decrease in the growth of multi-drug-resistant bacteria was reported in two papers ( p = 0.065 and p = 0.04). Conclusion: Intravesical gentamicin seems to be an effective treatment in patients with symptomatic rUTIs. The evidence suggests it also reduces UTIs caused by multi-drug-resistant bacteria with no systemic absorption and minimal renal toxicity. Level of evidence: 2a

Risk factors for breakthrough urinary tract infection in children with vesicoureteral reflux receiving continuous antibiotic prophylaxis.

BackgroundTo investigate the risk factors for breakthrough urinary tract infection (BT-UTI) in children with vesicoureteral reflux (VUR) receiving continuous antibiotic prophylaxis (CAP).MethodsThis was a single-centre cohort study (January 2016 to December 2019). The clinical data of 256 children with grade I–V VUR receiving CAP were analysed. In this study, exposure variables were sex, younger age at the initial diagnosis of UTI ≤12 months, high-grade VUR, bilateral VUR, aetiology, presence of renal scarring at the initial diagnosis, presence of renal function impairment at the initial diagnosis, ultrasound abnormalities, antibiotic used and bladder and bowel dysfunction (BBD). Outcome was BT-UTI.ResultsBT-UTI occurred in 81 out of 256 children with grade I–V VUR who received CAP, an incidence of 31.64%. Univariate analysis showed that younger age at the initial diagnosis of UTI (≤12 months), bilateral VUR, renal scarring on the dimercaptosuccinic acid (DMSA) scan at the initial diagnosis of UTI and BBD were correlated with the occurrence of BT-UTI. Multivariate analysis showed that younger age at the initial diagnosis of UTI (≤12 months) [hazard ratio (HR): 4.629; 95% confidence interval (CI): 1.302–16.462], bilateral VUR (HR: 2.078; 95% CI: 1.084–4.022) and BBD (HR: 3.194; 95% CI: 1.243–8.206) were independent risk factors for the occurrence of BT-UTI.ConclusionsFor VUR children receiving CAP, younger age at the initial diagnosis of UTI (≤12 months), bilateral VUR, and BBD were independent risk factors for the occurrence of BT-UTI.

MP25-18 OPTIMAL MANAGEMENT OF CONTINUOUS ANTIBIOTIC PROPHYLAXIS AFTER INITIAL BREAKTHROUGH UTI IN CHILDREN WITH VESICOURETERAL REFLUX

You have accessJournal of UrologyInfections/Inflammation/Cystic Disease of the Genitourinary Tract: Kidney & Bladder I (MP25)1 Sep 2021MP25-18 OPTIMAL MANAGEMENT OF CONTINUOUS ANTIBIOTIC PROPHYLAXIS AFTER INITIAL BREAKTHROUGH UTI IN CHILDREN WITH VESICOURETERAL REFLUX Lane Shish, and Kathleen Kieran Lane ShishLane Shish More articles by this author , and Kathleen KieranKathleen Kieran More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002022.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Continuous antibiotic prophylaxis (CAP) can reduce the risk of recurrent urinary tract infections (UTI) for children with vesicoureteral reflux (VUR). If a child has a breakthrough UTI (BT-UTI) while on CAP, current guidelines suggest surgical repair or continuing CAP after changing the agent. However, the latter option is based primarily on expert opinion. This study evaluated if switching the CAP agent after children had an initial BT-UTI changed the risk of a second-UTI compared to leaving CAP unchanged. We hypothesized that there was no difference in UTI recurrence in the cohort of patients in whom CAP agent was changed compared with those continued on the same CAP agent after BT-UTI. METHODS: We retrospectively identified all children aged 0-18 months with radiographically confirmed primary VUR and a BT-UTI while on CAP for UTI prevention between January 2013 and August 2020. Patient demographics, BT-UTI characteristics, time on CAP agents, and incidence and timing of second BT-UTI (when applicable) were collected. The primary outcome was the relative risk of a second BT-UTI in patients with CAP agent changed after the initial BT-UTI versus unchanged. The secondary outcome was the rate ratio of second BT-UTIs per person-years on CAP after the initial BT-UTI when the CAP agent was changed versus unchanged. RESULTS: Sixty-two patients were identified: 24 (38.7%) had CAP changed and 38 had CAP unchanged. A second BT-UTI developed in 12/24 children (50%) with CAP changed and in 22/38 children (57.9%) with CAP unchanged. The relative risk of a second BT-UTI when CAP was changed (versus unchanged) was 0.86 (p=0.55). The rate of second BT-UTIs when the CAP was changed was 12 cases per 18.34 person-years after the initial BT-UTI and 22 cases per 22.36 person-years after the initial BT-UTI when CAP was unchanged. The rate ratio of second BT-UTI in changed CAP cohort was 0.67 (p=0.25). Of the children in the changed CAP cohort with a second BT-UTI, 33.3% had developed resistance to both their initial and contemporary CAP agent. CONCLUSIONS: Changing a child’s UTI CAP after an initial BT-UTI did not significantly change the risk of a second BT-UTI compared to leaving CAP unchanged, while it did introduce a risk of developing a second UTI with increased antibiotic resistance. This suggests that, after an initial BT-UTI, changing CAP may not confer clinical benefit and may increase the prevalence of resistant micro-organisms. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e460-e461 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lane Shish More articles by this author Kathleen Kieran More articles by this author Expand All Advertisement Loading ...

Pneumovesicoscopic Correction of Primary Vesicoureteral Reflux in Children: Our Initial Experience.

Purpose: The main objective of our prospective, descriptive, monocentric, longitudinal study is to demonstrate the feasibility of vesicoscopic cross-trigonal ureteral reimplantation under CO2 pneumovesicum in treatment on primary vesicoureteral reflux (VUR), analyze results, and specify the age limit of this approach. Materials and Methods: A total of 60 patients underwent transvesicoscopic ureteral reimplantation (33 boys, 27 girls) by the same surgeon from May 2011 to May 2015. All patients had primary VUR, and surgery was performed because of breakthrough urinary tract infection despite antibiotic prophylaxis and persistent high grade of VUR, especially in association with significant renal scarring, mean age at operation was 47.47 months (6 month-12 years). Of the 60 patients, 34 had bilateral reflux and 26 had unilateral reflux. The reflux grade in the total of 94 ureters was grade IV, V in 59.57%, grade III in 35.11%, and grade II in 5.32% in association with contralateral high-grade VUR. Results: The transvesicoscopic procedure was effectively completed in all patients without perioperative complication except one case of pneumoperitoneum that required exsufflation by open laparoscopy. The mean overall operative time decreased significantly with an average of 58.43 ± 11.26 minutes for unilateral reimplantation and 101.18 ± 26.5 minutes for bilateral reimplantation. The postoperative hospital stay was 3 days for all patients. The mean follow-up period was 3 years. Cystography was performed 3 months after surgery in all patients and showed the disappearance of VUR in 57/60 patients (95%) or 91/94 of ureters (97%). Persistent VUR was documented in 3 of 94 ureters and had resolved spontaneously at 12 months after reimplantation. Conclusion: Our preliminary results indicate that vesicoscopic ureteral reimplantation is safe and effective procedure with minimal morbidity when compared to traditional open method. It can be applied in children younger than 12 months.

The additive impact of the distal ureteral diameter ratio in predicting early breakthrough urinary tract infections in children with vesicoureteral reflux

Many factors influence patient and provider decisions to surgically correct vesicoureteral reflux (VUR), including risk of breakthrough febrile urinary tract infections and likelihood of spontaneous resolution. Ureteral diameter ratio has been shown in several studies to be more predictive than reflux grade with regard to breakthrough urinary tract infection (UTI). We developed and investigated the accuracy of a computational model for predicating febrile breakthrough urinary tract infection within 13 months of starting prophylactic antibiotics in children with VUR. The aim of this study was to validate a model for evaluating the impact of distal ureteral diameter ratio (UDR) in predicting early breakthrough urinary tract infections in children with VUR. Following a retrospective review, we recorded patient demographics, presenting symptoms, VUR grade, laterality, VUR during filling or voiding, initial bladder volume at the onset of VUR, ureteral duplication, voiding dysfunction, distal ureteral diameter ratio, and number of UTIs prior to VUR diagnosis. NeUROn++, a set of C++ programs, was used to model each data set using logistic regression and neural networks with different architectures. After exclusions, 136 children (93 girls and 43 boys) diagnosed with primary VUR had detailed VCUG and UDR data available. Fourteen children (10.3%) experienced breakthrough febrile UTI events within 13 months of VUR diagnosis. There was a significant association with UDR and breakthrough UTI (p=0.008). Various computational prediction models for the outcome of breakthrough UTI were developed and evaluated. The computational model that fit best was a model using all variables with an ROC of 0.802. Clinicians and parents often opt for intervention based on likelihood of spontaneous resolution of VUR as well as clinical course, thereby placing an emphasis on the ability to predict likelihood of breakthrough UTI infections. Our statistical analysis and prediction models further confirm UDR as an important variable predictive of breakthrough UTIs within the first 13 months of beginning prophylactic antibiotics. Furthermore, we developed a neural network model incorporating UDR and grade with an ability to yield the greatest accuracy of any breakthrough UTI predictive calculator to date at 80%.

Conservative Management of Vesicoureteral Reflux

Vesicoureteral reflux (VUR) is defined as the retrograde flow of urine from the bladder to the upper urinary tract (the ureters and kidneys), caused by ureterovesical junction dysfunction. VUR is the most common congenital urinary tract abnormality; nevertheless, the conservative treatment for VUR remains controversial. In addition, the limited data availability made it difficult to establish a widely accepted treatment protocol. This study aimed to review available treatment modalities and recommendations with regard to the conservative management for VUR. An online literature search was performed on PubMed, PubMed Central, and Google Scholar. Studies were compared with several available guidelines. Based on literature search, the conservative management of VUR involves a multimodality approach, including the bladder-bowel dysfunction management through bladder training, anticholinergics and alpha-blockers, continuous antibiotic prophylaxis, and circumcision in male patients. Operative and other invasive treatment modalities may be considered in treatment failure or breakthrough urinary tract infection and should not be used as a first-line treatment.

Standardized protocol for voiding cystourethrogram: Are recommendations being followed?

Voiding cystourethrogram (VCUG) images the urethra and bladder during filling and emptying, as well as ureters and kidneys when vesicoureteral reflux (VUR) is present, providing detailed information about both anatomical and functional status of the urinary tract. Given the importance of information obtained, and the varying quality depending on VCUG technique and radiology reporting, the American Academy of Pediatrics Sections on Urology and Radiology published a joint standardized VCUG protocol in 2016. We compared VCUG reports from multiple institutions before and after publication of the protocol to determine adherence to recommendations. VCUG reports generated during two separate time periods were assessed - before and after publication - to evaluate impact of the protocol. Adherence to the reporting template was evaluated. Studies performed on patients >18 years of age and those obtained for trauma evaluation were excluded from study. A total of 3121 VCUG reports were analyzed, 989 (31.7%) were generated before and 2132 (68.3%) after protocol publication. Comparing cohorts, there was no difference in gender (62.6% female versus 61.4%; p = 0.53) though children in the post-cohort were slightly older (3.34 ± 3.82 versus 3.68 ± 4.19 years; p = 0.03). A significant increase in scout image reporting (91.5%) and cyclic studies (20.5%) were observed in the post-cohort, in comparison to 79.2% and 13.1%, respectively, in the pre-protocol cohort (p < 0.001) [Figure]. Measured PVR and recorded infused volume actually decreased between study periods (84.7% vs 72.8% and 97.2% vs 91.5%, p < 0.001). There was no statistically significant difference between VUR grade reporting (99.4 vs 98.5%, p = 0.25). Recorded volume in which reflux occurred increased between periods (0.6% vs 2.3%, p < 0.05), while reporting of filling vs voiding reflux decreased in the post-cohort (84.4% pre-vs 77.4% post-protocol, p < 0.008). The 2016 VCUG protocol recommended inclusion of various data points, however the volume at which reflux occurs remained vastly underreported. Timing of reflux has been shown to predict likelihood of spontaneous resolution and risk of breakthrough urinary tract infection; thus, its omission may limit the information used to counsel families and provide individualized care. Despite consensus on standard VCUG protocol to best perform and record data, reports remain inconsistent. While VUR grade is routinely reported, other important anatomic and functional findings which are known to impact resolution and breakthrough urinary tract infection rates, such as volume at which reflux occurs, are consistently underreported.

Adverse effects of chronic nitrofurantoin therapy in women with recurrent urinary tract infections in an outpatient setting.

To review the frequency of adverse events reported with nitrofurantoin (NF) in perimenopausal and menopausal women on prolonged daily prophylaxis in an outpatient setting. Electronic medical records of women aged 50-95 prescribed NF by 2 primary urology providers for at least 3 consecutive months from 2006 to 2018 were retrospectively reviewed. Demographics, reason for the initiation, dose and duration of therapy, explanation of therapy interruptions, occurrence of adverse events, comorbid conditions, and relevant lab and imaging results were recorded. The number of months on prolonged therapy were summed. Of the 221 patients included, 167 (77%) were prescribed 100mg of NF dailywith a mean duration of therapy of1.5years. The most common indication for therapywas recurrent urinary tract infection prophylaxis. Breakthrough urinary tract infections developed in 88 (40%) patients on prolonged NF therapy but only 10 were not restarted on NF. Four patients (1.8%) were determined to have pulmonary adverse events and 1 (0.4%) developed elevated liver function tests. In peri-menopausal and menopausal women, the risks and benefits of chronic NF therapyshould be weighed by the clinician and patient prior to prescribing long term NF. Patients must be educated about the potential NF toxicities and clinically monitored for signs and symptoms of potential adverse events while on chronic NF therapy.

Intravesical gentamicin instillation for the treatment and prevention of urinary tract infections in complex paediatric urology patients: evidence for safety and efficacy

Little has been reported to date on the instillation of antimicrobials directly into the bladder in children. Children with complex urinary tract anomalies struggle frequently with recurrent urinary tract infections (UTI), with frequent emergence of antibiotic resistance. Gentamicin bladder instillation to treat and prevent UTI was described in children since 2006. We adopted gentamicin bladder instillation in 2016 and evaluate herein our intermediate-term experience with it. This study is a retrospective review of a prospectively initiated database and a clinical audit of our practice. The gentamicin bladder instillation was employed in 24 cases. A treatment regime was initiated for symptomatic documented UTI when resistance patterns precluded an oral alternative (14 cases), avoiding hospitalisation for parenteral antibiotics. A prophylaxis regime (19 cases-including 9 of the 14 who received an initial treatment regime) followed at least one breakthrough UTI while receiving oral prophylactic antibiotics. Two instillation volumes (8mg gentamicin in 20mL 0.9% NaCl or 20mg gentamicin in 50mL 0.9% NaCl) were used to suit different bladder capacities. The irrigation is given twice a day for 7 days in the treatment regime or once a day, every other day, in the prophylactic regime. Gentamicin serum levels (all cases) and audiology/audiometry testing (17/24 cases) were checked to assess the safety of this method. The median age when either the treatment course or prophylaxis regime was started was 3.8 years. The treatment regime was 86% successful (12/14) to suppress an acute UTI. The mean duration of prophylaxis was 252 days (median: 256 days). The percentage of patients on the prophylactic regime who had no breakthrough UTI was 58%. No serum gentamicin was detectable secondary to the intravesical instillation. No attributable cases of sensorineural hearing loss were detected. Gentamicin resistance emerged in one case (4.16%). Intravesical administration was feasible via various routes for a spectrum of complex lower urinary tract abnormalities (see Summary Figure). Concerns regarding systemic absorption, nephrotoxicity or ototoxicity were investigated and safety ensured. Limitations include being a small series of non-identical pathologies, albeit categorically similar and being a single-arm study, however, statistical significance was proven descriptively and analytically. In selected cases and with the appropriate specialist support and logistics, intravesical gentamicin instillation is well-tolerated and safe to treat and/or prevent urinary tract infections in pateints with complex bladder conditions and lower urinary tract pathologies.

A scoring system for predicting downgrading and resolution of high-grade infant vesicoureteral reflux.

Aim of the study was to provide a scoring system for predicting downgrading and resolution of infantile high-grade vesicoureteral reflux (VUR). Eighty-nine infants (65 boys) with high-grade VUR (grade 4-5) diagnosed at median age 2.5months and followed to 39months had repeated investigations of VUR grade, renal damage/function and bladder function. Recurrent urinary tract infections (UTIs) were registered. Risk variables collected at 1year were analysed as independent factors for spontaneous resolution to grades ≤2 and 0, using univariable/multivariable logistic regression. A scoring system was built with a total of 14 points from four independent risk factors (sex, breakthrough UTI, type of renal damage and subnormal glomerular filtration rate). Children with persistent VUR (grade 3-5) had higher scores compared with the group with spontaneous resolution (grade 0-2) (mean 7.9 vs. 4.5, P<.0001). A score of ≥8 points indicated a low probability of VUR resolution (≤14%). The model was considered excellent based on area under the ROC curve (0.82) and showed satisfactory internal validity. This model provides a practical tool in the management of infants born with high-grade reflux. High scores at one year of age indicate a high risk of persistent dilated reflux.

Antibiotic prophylaxis for prevention of urinary tract infections in the first year of life in children with vesicoureteral reflux diagnosed in the workup of antenatal hydronephrosis: a systematic review.

Children with antenatal hydronephrosis (ANH) diagnosed with postnatal asymptomatic vesicoureteral reflux (VUR) are thought to be at higher risk of urinary tract infection (UTI). As such, continuous antibiotic prophylaxis (CAP) is empirically recommended until age of toilet training; however, there are limited data to support this. The objective of this systematic review was to summarize the existing data and compare UTI rates in infants with asymptomatic VUR on CAP during the first year of life, to those not on CAP. Secondary objectives were to determine associated risk factors with UTI development. A systematic search of all relevant studies and abstracts was conducted using 4 electronic databases by utilizing appropriate key words by an expert hospital librarian. Eligible studies included children with prenatal hydronephrosis, asymptomatic VUR with or without CAP, and reported on development of UTI in the first year. Of 6903 citations screened, 18 were selected, giving a total population of 829 (69.4% male, median age 57days) who met the inclusion criteria. Most studies were retrospective and of low-quality evidence. Overall, 15.4% of patients developed at least one breakthrough UTI and females had a higher risk of UTI (odds ratio (OR) 2.3, 95% CI 1.1-4.7). Comparison with children not taking CAP was not readily reported, and meta-analysis could not be completed. Randomized controlled trials and standardized reporting of clinical variables are required to understand the protective effect of antibiotic prophylaxis in this cohort.

Predicting Breakthrough Urinary Tract Infection: Comparative Analysis of Vesicoureteral Reflux Index, Reflux Grade and Ureteral Diameter Ratio.

The vesicoureteral reflux index is a simple, validated tool for predicting resolution of reflux. Along with likelihood of spontaneous resolution identification of children at risk for febrile urinary tract infection impacts management. We evaluated the usefulness of the vesicoureteral reflux index as a predictive factor for breakthrough febrile urinary tract infection compared to reflux grade and distal ureteral diameter ratio. Children with primary vesicoureteral reflux and detailed voiding cystourethrogram data were identified. A 1 to 6-point index was assigned, and ureteral diameter ratio was computed by measuring largest ureteral diameter within the pelvis and dividing by the distance between L1 to L3 vertebral bodies. Random forest modeling and logistic multivariable regression were employed to estimate the predictive ability of grade, ureteral diameter ratio and vesicoureteral reflux index with regard to breakthrough febrile urinary tract infection. We analyzed 94 girls and 45 boys with a mean±SD age of 5.4±4.7 months at diagnosis. Mean±SD length of followup was 32.1±24.5 months. A total of 13 children (9.4%) experienced breakthrough febrile urinary tract infection. On univariate analysis ureteral diameter ratio (p=0.01) and vesicoureteral reflux index (p=0.0005) were associated with breakthrough urinary tract infection, while grade (p=0.09) did not reach significance. Area under the curve was generated as a measure of accuracy for each variable and was 0.77 for the vesicoureteral reflux index, 0.71 for ureteral diameter ratio and 0.68 for grade, indicating superiority of the vesicoureteral reflux index for predicting breakthrough febrile urinary tract infection. Children with higher vesicoureteral reflux index are at increased risk for breakthrough febrile urinary tract infection independent of reflux grade. The vesicoureteral reflux index provides valuable prognostic information about infection risk, facilitating improved clinical decision making.

Renal scarring is the most significant predictor of breakthrough febrile urinary tract infection in patients with simplex and duplex primary vesico-ureteral reflux

The association of high-grade vesico-ureteral reflux (VUR) with renal dysplasia and/or scarring is well-established, and the combination of these factors has been shown to decrease the likelihood of VUR resolution. Other VUR parameters have similarly been shown to be associated with VUR non-resolution, including VUR grade and timing at cystography, associated urinary tract anatomical abnormalities, and bladder dysfunction. To establish independent risk factors that can predict symptomatic persistence of VUR. This was a single-centre study (2011-2017) including consecutive prospectively collected patients with primary VUR on voiding cystourethrogram (VCUG). Patients with dilating VUR also underwent renography (dimercaptosuccinic acid [DMSA] or 99m-technetium mercaptoacetyltriglycine [99mTc-MAG3]). All patients were initially managed medically with antibiotic prophylaxis. Primary outcome was febrile culture-positive breakthrough urinary tract infection (BT-UTI). Demographic parameters, as well as VUR grade, VUR timing at cystography, presence of ureteral anomaly, VUR index (VURx), and differential renal function (DRF) or scarring were analysed to determine independent predictors. A total of 61 patients (41 male, of whom 7 circumcised at presentation) were studied. VUR was diagnosed following investigation of prenatal hydronephrosis in 37 patients (62%) and following a febrile UTI in 22 (37%). Median [range] follow-up period was 38 [12-84]months. Data from a total of 77 refluxing renal units (RUs) were used for analysis. Analysis of VCUG data demonstrated that high VURx might be a potential significant predictor of breakthrough UTI (RR: 1.7, 95% CI: 1.1-2.7, p<0.05 vs low VURx) but this was not the case for individual VURx components. Renography data showed increased risk of breakthrough UTI in patients with renal scarring (relative risk (RR): 5.1, 95% confidence interval (CI: 2.0-10.7, p<0.0001 vs no renal scarring), but not in patients with reduced DRF. Multivariate regression analysis revealed that renal scarring was the only significant risk factor for breakthrough UTI. VUR patients with renal scarring were three times more likely to develop breakthrough UTI (odds ratio (OR): 3.3, 95% CI: 1.4-7.4, p<0.01). Multiple factors have been shown to be significant predictors of radiological VUR resolution. Univariate analysis of these factors suggests that only scarring on DMSA and VURx are significant predictors of symptomatic non-resolution. On multivariate analysis, scarring on DMSA was the only significant predictive variable. This information will be useful in targeting investigation and treatment in susceptible patients and when counselling families. Renal scarring is the most significant risk factor for breakthrough UTI in primary VUR patients and could be used to determine those at risk of symptomatic VUR persistence.

Is a Drainage Placement Still Necessary After Robotic Reconstruction of the Upper Urinary Tract in Children? Experience from a Tertiary Referral Center.

Purpose: To compare the surgical outcomes of children submitted to robot-assisted reconstruction with or without drainage placement performed by a single surgeon in a tertiary referral center. Materials and Methods: Patients submitted to robot-assisted reconstruction, including pyeloplasty for ureteral pelvic junction obstruction, end-to-end anastomosis for retrocaval ureter, and reimplantation for vesical ureter reflux (VUR) from January 2016 to November 2018, were included. Patients with ureteral pelvic junction obstruction or retrocaval ureter were selected for surgery according to the presence of symptoms and/or evidence of obstruction on diagnostic imaging. The criteria for reimplantation included breakthrough urinary tract infections, progressive renal scarring, and persistent VUR despite watchful waiting. Results: Overall, 31 children composed the no drain placement (DP) group and 29 the DP group. Preoperative feature of the two groups were comparable. Overall, only 1 (3.3%) postoperative complication occurred in no DP group and 2 (6.9%) in the placement group (P = .512). Length of stay was 3 (interquartile range [IQR]: 3-4) and 4 (IQR: 4-4) days, respectively (P = .651). At last follow-up, overall success rate was 100% in the no DP group and 96.6% in the DP group (P = .297). Conclusions: Robot-assisted reconstruction represents a safe minimally invasive approach with optimal surgical outcomes for the treatment of upper urinary tract. Expert robotic surgeons could avoid drainage placement after surgery as this does not undermine perioperative outcomes and postoperative success rate. Our study, first in literature, proves the interest in assessing the safety of no drainage placement also in the pediatric field.

IJU this issue

IJU this issue