Effect of Dose Timing of Coupled Intravesical Gentamicin and Lactobacillus Rhamnosus LGG on Success and Length of Colonization in Men and Women With SCI/D and NLUTD
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 48
- 试验地点
- 2
研究概览
简要总结
The main objective of the proposed research study is to determine in men and women with spinal cord injury/disease and neurogenic bladder whether the dose of coupled gentamicin & Lactobacillus rhamnosus GG affects the recolonization of the bladder, and whether the rate of success differs by sex. Secondary objectives include determining whether that recolonization lasts 7, 14, or 28 days; and safety of the coupled gentamicin & Lactobacillus instillations.
详细描述
People with spinal cord injury/disease (SCI/D) experience, on average, 2.5 episodes of UTI annually. Since repeated exposures of bacteria to antibiotics leads to multi-drug resistant organisms (MDROs), it is likely that the frequent use of antibiotics for UTI is a driver of the increasing prevalence of infections with MDROs in the SCI/D population. This prevalence of MDROs among people with SCI/D represents a microcosm of the world-wide public health crisis of antibiotic resistance. As stated by the CDC, "antibiotic resistance is one of the biggest public health challenges of our time." In the US alone, 2.8M people annually develop infections with resistant microbes; of whom 35,000 die as a direct result. Infections with resistant organisms are associated with longer hospital lengths of stay, increased mortality, and higher health care costs. With UTI persistently being the leading reason for rehospitalizations among people with SCI/D, infections with resistant organisms represent a contributor to elevated health care costs as well as mortality risk. Additionally, the cost to treat a UTI due to an extended-spectrum beta-lactamase (ESBL) organism is estimated to be 1.5 times greater than treating a non-ESBL pathogen. Thus, not only are people with SCI/D and UTI at greater risk of mortality due to MDROs, they are also likely to have higher costs as a result of UTI. These costs can only be expected to increase, as the rate of antibiotic resistant UTIs increases. Moreover, individuals with SCI/D and NLUTD experience lower urinary tract symptoms (LUTS) frequently, and these may be treated with antibiotics whether they represent UTI or not.
As noted earlier, the standard of care for UTI treatment (systemic antibiotics, guided by standard urine culture (SUC)) is flawed and contributes to overtreatment and antimicrobial resistance. Use of intravesical therapeutics have been a part of clinical practice since the 1960's and intravesical antibiotics have been studied for nearly 30 years; however, use of intravesical antibiotics for UTI is typically only considered as a "last resort" (such as for recurrent UTI). Agents used include gentamicin, tobramycin, colistin, and neomycin/polymyxin. Gentamicin is the most commonly studied intravesical antibiotic and when administered intravesicularly, it has been shown to have little to no systemic absorption, nor nephro- or oto-toxicity (as with intravenous administration). Intravesical gentamicin has been shown to be safe, tolerated, and effective for recurrent UTI in people with NLUTD.
The investigators' team was first to compare the urobiomes of people with SCI/D and NLUTD to those of neurologically intact controls. This work verified the existence of the urobiome, showing that most control female urobiomes are predominated by Lactobacillus and some control male urobiomes contain Lactobacillus, but most do not. The investigators also showed that NLUTD urobiomes are dysbiotic, depleted in beneficial bacteria as most NLUTD females lacked or had reduced Lactobacillus levels, while most NLUTD males lacked the Streptococcus and/or Corynebacterium that was commonly observed in control males. These results support the investigators' hypothesis that NLUTD bladders of most females and at least some males could be colonized by LGG, and that LGG in the urobiome could improve urinary symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Neurologic diagnosis
- •≥18 years old
- •Neurogenic bladder for at least 6 months
- •No USQNB-IC A, B1, or B2 symptoms
- •No currently diagnosed UTI (within 24 hours of initiating instillations)
- •Community dwelling (not in acute hospital setting)
排除标准
- •Known genitourinary pathology beyond NLUTD (i.e. kidney stones, bladder stones, vesicoureteral reflux, etc.)
- •Use of prophylactic antibiotics or any antibiotics within 2 weeks of beginning instillations
- •Instillation of intravesical agents other than saline bladder wash
- •Immunodeficiency
- •Psychologic or psychiatric conditions influencing the ability to follow instructions
- •Allergy to ampicillin, daptomycin, gentamicin/gentamycin, or probiotics
- •Participation in another study which could confound results
研究组 & 干预措施
Low Dose
Gentamicin will be diluted in normal saline under sterile conditions by qualified pharmacy personnel to a concentration of 0.96mg/mL. 50cc (48 mg) of the resulting solution will be drawn up into a catheter tip syringe, which will then be capped and inserted into sterile packaging. Seven such syringes will be overnight mailed to each participant in temperature-controlled shipping containers. Once ready to begin instillations, the full contents of one syringe will then be instilled into the bladder after drainage of urine is complete by catheterization; the solution will be left indwelling until the next catheterization. This will be done six times. Low dose participants will wait 72 hours, then mix one capsule LGG into 45mL sterile saline and instill the resulting mixture in the same fashion as the gentamicin. Low dose participants will do this in once in the evening and again 12 hours later (the following morning). This mixture will remain in the bladder for at least 4 hours.
干预措施: Gentamicin (Drug)
High Dose
Gentamicin will be diluted in normal saline under sterile conditions by qualified pharmacy personnel to a concentration of 0.96mg/mL. 50cc (48 mg) of the resulting solution will be drawn up into a catheter tip syringe, which will then be capped and inserted into sterile packaging. Seven such syringes will be overnight mailed to each participant in temperature-controlled shipping containers. Once ready to begin instillations, the full contents of one syringe will then be instilled into the bladder after drainage of urine is complete by catheterization; the solution will be left indwelling until the next catheterization. This will be done six times. High dose participants will wait 72 hours, then mix one capsule LGG into 45mL sterile saline and instill the resulting mixture in the same fashion as the gentamicin. High dose participants will do this in once in the evening, and again every 12 hours until four doses are complete. This mixture will remain in the bladder for at least 4 hours.
干预措施: Gentamicin (Drug)
High Dose
Gentamicin will be diluted in normal saline under sterile conditions by qualified pharmacy personnel to a concentration of 0.96mg/mL. 50cc (48 mg) of the resulting solution will be drawn up into a catheter tip syringe, which will then be capped and inserted into sterile packaging. Seven such syringes will be overnight mailed to each participant in temperature-controlled shipping containers. Once ready to begin instillations, the full contents of one syringe will then be instilled into the bladder after drainage of urine is complete by catheterization; the solution will be left indwelling until the next catheterization. This will be done six times. High dose participants will wait 72 hours, then mix one capsule LGG into 45mL sterile saline and instill the resulting mixture in the same fashion as the gentamicin. High dose participants will do this in once in the evening, and again every 12 hours until four doses are complete. This mixture will remain in the bladder for at least 4 hours.
干预措施: Lactobacillus Rhamnosus GG (Drug)
Low Dose
Gentamicin will be diluted in normal saline under sterile conditions by qualified pharmacy personnel to a concentration of 0.96mg/mL. 50cc (48 mg) of the resulting solution will be drawn up into a catheter tip syringe, which will then be capped and inserted into sterile packaging. Seven such syringes will be overnight mailed to each participant in temperature-controlled shipping containers. Once ready to begin instillations, the full contents of one syringe will then be instilled into the bladder after drainage of urine is complete by catheterization; the solution will be left indwelling until the next catheterization. This will be done six times. Low dose participants will wait 72 hours, then mix one capsule LGG into 45mL sterile saline and instill the resulting mixture in the same fashion as the gentamicin. Low dose participants will do this in once in the evening and again 12 hours later (the following morning). This mixture will remain in the bladder for at least 4 hours.
干预措施: Lactobacillus Rhamnosus GG (Drug)