Periprocedural antibiotics for urodynamic studies of pediatric neurogenic bladder, empiric or culture-guided? A retrospective cohort study.

INTRODUCTION: Urodynamic studies are fundamental in the care of children with neurogenic bladder. Children with neurogenic bladder who perform clean intermittent catheterization (CIC) are considered a high-risk group for infection after urodynamic studies. Current guidelines are not uniform regarding the duration, type, the need of prophylactic antibiotic treatment or performance of urine culture before urodynamic studies. OBJECTIVE: To assess whether antibiotic prophylactic therapy before urodynamic studies should be empiric or culture-guided in children with neurogenic bladder who perform CIC. STUDY DESIGN: Urine samples were collected from children with neurogenic bladder who require CIC before undergoing a urodynamic study. Urine cultures were collected via sterile urethral catheterization one week before urodynamic studies between 2010 and 2018. Children with signs of urinary tract infection (UTI) or children with bladder augmentation were excluded. Resistance to commonly prescribed periprocedural antibiotic treatments was documented. The probability of antibiotic resistance according to sex, vesicoureteral reflux (VUR) status, consumption of prophylactic antibiotics, and self/caregiver performed CIC was determined by a χ2-test. RESULTS: A total of 278 urine cultures were collected from 185 children with neurogenic bladder. The median age was 8 years (IQR 5-12). The most common etiology for neurogenic bladder was spinal dysraphism (n = 146, 77%). Bacterial growth was detected in 216 (78%) cultures, and the most commonly detected bacterial species was Escherichia. coli (n = 155, 72%). Thirty-six (19%) children had VUR, and 14 of them received continuous prophylactic antibiotics. The probability of resistance to oral antibiotics was amoxicillin (22%), cephalexin (21%), cefuroxime (14%), ciprofloxacin (10%), nitrofurantoin (21%), and sulfamethoxazole/trimethoprim (SMX/TMP) (23%) (See "summary table") No significant differences were found by χ2-test in the probability of resistance to antibiotics according to sex, VUR status, continuous antibiotic prophylaxis or self/caregiver performed CIC. DISCUSSION: The study reveals high resistance level to commonly prescribed oral antibiotic treatments (20-30%). Several studies have challenged the need of routine urine cultures before urodynamic studies due to low risk of post-procedural infection. However, it should be mentioned that not all the patients participating in those studies were with neurogenic bladder or routinely performed CIC. Hence, in this specific group of children, routine urine cultures should not be abandoned. The limitations of the study are: Single-center, retrospective study with no data availability regarding the development of UTI after the urodynamic studies. CONCLUSIONS: Urine cultures of children with neurogenic bladder who require CIC demonstrate significant levels of resistance to commonly prescribed oral antibiotics. These findings support culture-guided periprocedural antibiotic prophylaxis.

Asymptomatic bacteriuria and antibiotic resistance profile in children with neurogenic bladder who require clean intermittent catheterization.

STUDY DESIGN: A retrospective cohort study. OBJECTIVES: To document the prevalence of asymptomatic bacteriuria and to characterize the resistance patterns to antibiotics among children with neurogenic bladder who require clean intermittent catheterization, with an emphasis on multidrug resistance. SETTING: A national referral pediatric and adolescent rehabilitation facility in Jerusalem, Israel. METHODS: Routine urine cultures were collected before urodynamic studies in suitable individuals during 2010-2018. None of them had symptoms of urinary tract infection at the time of specimen collection. Cultures were defined as being positive if a single bacterial species was isolated together with a growth of over 105 colony-forming units/ml. Resistance patterns were defined as extended-spectrum beta-lactamase (ESBL) and resistant to 3 antimicrobial groups (multi-drug resistant, MDR). RESULTS: In total, 281 urine cultures were available for 186 participants (median age 7 years, range 0.5-18). Etiologies for CIC included myelomeningocele (n = 137, 74%), spinal cord injury (n = 16, 9%) and caudal regression syndrome (n = 9, 5%). Vesicoureteral reflux was diagnosed in 36 participants (19%), 14 of whom were treated with prophylactic antibiotics. Asymptomatic bacteriuria was present in 217 specimens (77%, 95%CI [0.72-0.82]). The bacteria species were E. coli (71%), Klebsiella (13%), and Proteus (10%). ESBL was found in 11% of the positive cultures and MDR in 9%, yielding a total of 34 (16% of positive cultures) positive for ESBL and/or MDR bacteria. CONCLUSIONS: Asymptomatic bacteriuria and resistance to antimicrobials are common in pediatric individuals who require CIC.

Do formulation differences between the reference listed drug and generic piperacillin-tazobactam impact reconstitution?

Pharmaceutical differences between the reference listed drug (RLD) and generic formulations of piperacillin-tazobactam may impact the reconstitution process for intravenous administration. This study evaluated the RLD against three generic formulations and measured their reconstitution times using a standardized process. The mean (standard deviation [SD]) reconstitution time for one generic formulation was 5.57 (1.49) min, which was 35% to 42% longer (P < 0.002) than that for the RLD and two other formulations. Observable microscopic differences in powder particle morphology may explain these findings.

Application of modeling to scale-up dissolution in pharmaceutical manufacturing.

Liquid mixing scale-up in pharmaceutical industry has often been based on empirical approach in spite of tremendous understanding of liquid mixing scale-up in engineering fields. In this work, we attempt to provide a model-based approach to scale-up dissolution process from a 2 l lab-scale vessel to a 4,000 l scale vessel used in manufacturing. Propylparaben was used as a model compound to verify the model predictions for operating conditions at commercial scale that would result in similar dissolution profile as observed in lab scale. Geometric similarity was maintained between both of the scales to ensure similar mixing characteristics. We utilized computational fluid dynamics (CFD) to ensure that the operating conditions at laboratory and commercial scale will result in similar power per unit volume (P/V). Utilizing this simple scale-up criterion of similar P/V across different scales, results obtained indicate fairly good reproducibility of the dissolution profiles between the two scales. Utilization of concepts of design of experiments enabled summarizing scale-up results in statistically meaningful parameters, for example -90% dissolution in lab scale at a given time under certain operating conditions will result in 75-88% at commercial scale with 95% confidence interval when P/V is maintained constant across the two scales. In this work, we have successfully demonstrated that scale-up of solid dissolution can be done using a systematic process of lab-scale experiments followed by simple CFD modeling to predict commercial-scale experimental conditions.