Objective To determine the safety and tolerability of self-instilled intravesicular probiotic - PowerPoint Presentation

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Objective

To determine the safety and tolerability of self-instilled intravesicular probiotic

Lactobacillus via intermittent catheterization for urinary symptoms in individuals with Spinal Cord Injury (SCI) or Spina Bifida (SB). IntroductionUrinary Tract Infection(UTI) is the most common infection for people with spinal cord injury and catheter acquired UTIs are the most common hospital acquired infection world-wide.1-3 While it is essential to reduce the impact of UTIs the definition of a UTI among people with Spinal Cord Injury (SCI) remains unclear, including; a) the symptoms that can reliably indicate UTI;4-6 b) the degree of inflammatory reaction that differentiates UTI from other infectious urinary conditions;7-8 and c) bacterial load (determined by urine culture) to confirm and guide treatment for UTI.9-10 Due to the lack of evidence-based guidelines for determination of UTI, diagnosis is largely subjective and highly variable amongst practitioners likely contributing to over-treatment of UTIs.11Methods103 individuals (96 adults and 7 children) with SCI or Spina Bifida (SB) were enrolled in a prospective 18-month, 3 stage study (6 months each: baseline, intervention, follow-up) assessing the safety and tolerability of intravesicular Lactobacillus self-instilled in response to select symptoms. Symptoms were monitored weekly using our newly developed Urinary Symptom Questionnaire for Individuals with Neuropathic Bladder/Intermittent Catheterization version (USQNB-IC) (See Figure 1). All subjects received training on when and how to prepare the Lactobacillus solution and how to instill the solution via their intermittent catheter. Upon onset of cloudier or more foul smelling urine than usual, participants used the Self-Management Protocol using Probiotics (SMP-PRO) (See Figure 2) to determine when to instillation Lactobacillus. If guided to instill Lactobacillus due to cloudy or more foul-smelling urine, participants used a new catheter to instill the Lactobacillus solution after emptying their bladder. Cloudy or foul smelling urine was determined to be the symptoms that the intervention was targeting as these symptoms alone are not

Intravesical Lactobacillus is Safe and Well-Tolerated in Adults and Children with Neurogenic Bladder due to Spinal Cord Injury and Spina Bifida

References1 Cardenas DD, Moore KN, Dannels-McClure A, et al. Intermittent catheterization with a hydrophilic-coated catheter delays urinary tract infections in acute spinal cord injury: a prospective, randomized, multicenter trial. PM R. 2011;3(5):408-417. doi:10.1016/j.pmrj.2011.01.0012. Haisma JA, van der Woude LH, Stam HJ, et al. Complications following spinal cord injury: occurrence and risk factors in a longitudinal study during and after inpatient rehabilitation. J Rehabil Med. 2007;39(5):393-398. doi:10.2340/16501977-006 3.Plowman, R., Graves, N., Esquivel, J. & Roberts, J. A. An economic model to assess the cost and benefits of the routine use of silver alloy coated urinary catheters to reduce the risk of urinary tract infections in catheterized patients. J. Hosp. Infect. 48, 33–42 (2001).4. Disability, N. I. on & Rehabilitation Research Consensus Statement January 27–29, 1992. The Prevention and Management of Urinary Tract Infections Among People With Spinal Cord Injuries. J. Am. Paraplegia Soc. 15, 194–207 (1992).5. Hooton, T. M. et al. Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin. Infect. Dis. 50, 625–663 (2010)6. Hooton, T. M. et al. Diagnosis, Prevention, and Treatment of Catheter-Associated Urinary Tract Infection in Adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin. Infect. Dis. 50, 625–663 (2010).7. Vaidyanathan S, Soni BM, Dundas S, Krishnan KR. Urethral cytology in spinal cord injury patients performing intermittent catheterisation. Paraplegia. 1994;32(7):493-500. doi:10.1038/sc.1994.788. Schlager TA, Grady R, Mills SE, Hendley JO. Bladder epithelium is abnormal in patients with neurogenic bladder due to myelomeningocele. Spinal Cord. 2004;42(3):163-168. doi:10.1038/sj.sc.31015659. Groah S, Perez-Losada M, Caldovic L, et al. MP20-08 Pyuria and asymptomatic bacteriuria is associated with novel and specific urine microbiomes. The Journal of Urology. 2015;193(4):e226. doi:10.1016/j.juro.2015.02.98010. Jayawardena V, Midha M. Significance of bacteriuria in neurogenic bladder. J Spinal Cord Med. 2004;27(2):102-10511. Pannek J. Treatment of urinary tract infection in persons with spinal cord injury: guidelines, evidence, and clinical practice. The Journal of Spinal Cord Medicine. 2011;34(1):11-15. doi:10.1179/107902610X1288626109183912. Infectious Diseases Society of America. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. Mar 1 2010;50(5):625-663.

Figures

Figure 1: Urinary Symptoms Questionnaire for Neurogenic Bladder - Intermittent Catheterization

Limitations/Next Steps

Due to a small number of children participating in the study, we can only draw preliminary conclusions about the safety and tolerability in children.

For the adult population, next steps include assessing efficacy and determining optimal dosing for the intravesical

Lactobacillus.

Author

Inger Ljungberg, MPH

1,2; Suzanne Groah, MD, MSPH1; Amanda Rounds, PhD1,2; Bruce Sprague, BS3; Crystal Stroud, MS3; Hans Pohl, MD3; Ljubica Caldovic, PhD3; Michael Hsieh, MD31 MedStar National Rehabilitation Hospital Washington, DC 2 MedStar Health Research Institute Hyattsville, MD 3 Children’s National Medical Center Washington, DC

indicative of Urinary Tract Infection (UTI) according to the Infectious Diseases Society of America guidelines

12 , but may be a precursor to UTI and are the most frequently reported urinary symptoms. If urinary symptoms persisted 22-30 hours after first instillation, participants were advised to perform a second instillation.ResultsOf the 103 individuals, 79 (73 adults, 6 children) completed the study. During the intervention 69 (87.3%) (64 adults, 5 children) participants instilled Lactobacillus at least once ranging from 1-41 instillations per participant. Of the 357 instillations, there were 4 (1.1%) episodes of discomfort; 1 emotional discomfort due to a UTI; 1 stinging and irritation of the bladder/urethra post instillation); 1 UTI and kidney infection after one initiation (no Lactobacillus grew on urine culture); and 1 migraine after instillation. These instillations all occurred in adults and were classified as moderate adverse events (AE). A total of 59 adverse events (AEs) were reported during the study; 46 of which were serious AEs (SAE). 20 (43.5%) of the SAEs reported were Genitourinary (GU) in origin (17 upper or lower UTIs, 2 kidney infections and 1 prostate infection). The others were unrelated to the GU tract (see table 1). 4 GU SAEs (8.7%) occurred after Lactobacillus instillation. Of these, there were none with any amount of Lactobacillus growth. All were determined to be “unlikely related to Lactobacillus” by an external and independent Data Safety Monitoring Board. Table 1: Adverse events by organ system

ConclusionsOne or two doses of self-instilled intravesicular Lactobacillus when experiencing cloudier or more foul smelling urine than normal is safe and well-tolerated in adults with neurogenic bladder due to SCI and SB. Preliminary data suggests that one or two doses of self-instilled intravesical Lactobacillus is safe and well tolerated in children with neuropathic bladder due to SCI or SB.

AcknowledgementsThis work was supported by Patient Centered Outcomes Research Institute (PCORI) #AD1310-08215.Thank you to our six consumer experts working closely with the research team on this study

Figure 2: Self-Management Protocol using Probiotics