Pyeloplasty with ureteral stent placement in children: Do prophylactic antibiotics serve a purpose?

OBJECTIVES: Ureteral stents are commonly used during pyeloplasty to ensure drainage and anastomotic healing. Antibiotic prophylaxis is often used due to concerns for urinary tract infection (UTI). Although many surgeons prescribe prophylactic antibiotics following pyeloplasty, practices vary widely due to lack of clear evidence-based guidelines. We hypothesize that the rate of stent UTI does not significantly vary between children who receive antibiotics and those who do not. METHODS: We reviewed the medical records of 741 patients undergoing pyeloplasty between January 2010 and July 2018 across seven institutions. Exclusion criteria were: age older than 22 years, no stent placed, externalized stents used, and incomplete records. Surgical approach, age, antibiotic use, stent duration, Foley duration, and urine culture results were recorded. Patients were categorized into two groups, those younger than four years of age and those four years and older as proxy for likely diaper use. Univariate logistic regression was conducted to identify variables associated with UTI. Multivariable backward stepwise logistic regression was used to identify the best model with Akaike information criterion as model selection criteria. The selected model was used to calculate odds ratios and 95% confidence intervals summarizing the association between prophylactic antibiotics and stent UTI while controlling for age, gender, and intra-operative urine cultures. RESULTS: 672 patients were included; 338 received antibiotic prophylaxis and 334 did not. These groups differed in mean age (3.91 vs. 6.91 years, P < .001), mean stent duration (38.5 vs. 35.32 days, P < .001), and surgical approach (53.25% vs. 32.04% open vs. laparoscopic, P < .001). The incidence of stent UTI was low overall (7.59%) and similar in both groups: 31/338 (9.17%) in the prophylaxis group and 20/334 (5.99%) in the non-prophylaxis group (P = .119). Although female gender, likely diaper use, and positive intra-operative urine culture were each associated with significantly higher odds of stent UTI, prophylactic antibiotic use was not associated with significant reduction in stent UTI in any of these groups. Surgical approach, stent duration, and Foley duration were not associated with stent UTI. CONCLUSION: Incidence of stent UTI is low overall following pyeloplasty. Prophylactic antibiotics are not associated with lower rates of stent UTI following pyeloplasty even after controlling for risk factors of female gender, likely diaper use, and positive intra-operative urine culture. Routine administration of prophylactic antibiotics after pyeloplasty does not appear to be beneficial, and may be best reserved for those with multiple risk factors for UTI.

Applicability of image analysis to support QbD driven development of pellets.

OBJECTIVE: The stages of preparing high drug loaded pellets were investigated using static and dynamic imaging techniques to provide a greater understanding and ease the scale up process. SIGNIFICANCE: An example of a real case laboratory and production scale quality by design (QbD) based development of pellets is demonstrated. Potential process analytical technology (PAT) approaches by dynamic image analysis (DIA) are presented in various process phases. METHODS: Pellets were prepared at laboratory and production scale (high shear granulation, extrusion/spheronization, drying, and coating). The influence of process parameters on pellet properties (aspect ratio (AR), yield, pellet size, and their distribution) was investigated using static and DIA. During coating, we focused on the coating thickness and identification of potential agglomeration. RESULTS AND CONCLUSION: The effects of kneading time, amount of water, extrusion screen plate (ESP) opening diameter and thickness on pellet properties were confirmed in accordance with literature. In terms of screw speed, spheronization speed and time, no considerable influence on pellet properties was observed in the range of studied process parameters, thereby confirming the design space. In addition to the ESP thickness and opening diameter, quality of the ESP impacts the pellet properties. Lastly, coating thickness measurements with dynamic and static image analysis were comparable and an exemplary case of in-line agglomeration detection was presented. Real-time evaluation with PATVIS APA is an effective PAT tool for the evaluation of spheronization (pellet size distribution, AR, and yield) and coating (coating thickness, agglomeration detection).

Elucidating molecular properties of kappa-carrageenan as critical material attributes contributing to drug dissolution from pellets with a multivariate approach.

Multivariate data analysis (MVDA) and artificial neural networks (ANN) are supporting statistical methodologies required for successful development and manufacturing of drug products. To address this purpose, a complex dataset from 49 industrially produced capsules filled with pellets was first analyzed through the development of a multiple linear regression model focused on determining raw material attributes or process parameters with a significant impact on drug dissolution. Based on the model, the following molecular and micrometrics properties of κ-carrageenan have been identified as critical material attributes with the highest contribution to drug dissolution: molecular weight and polydispersity index, viscosity, content of potassium ions, wettability, particle size, and density. The process parameters identified to control the drug dissolution behavior of pellets were amount of granulation liquid, torque of dry blend, spheronization parameters, and yields after screening. To further scrutinize the dataset, an ANN model was subsequently built, incorporating 29 batches addressing drug particle size and process parameters such as torque during granulation and spheronization time as critical factors. Finally, this study demonstrates the ability of MVDA and ANN to allow prediction of the key performance drivers influencing the drug dissolution of industrially developed capsules filled with pellets and it highlights their complementary relationship.