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Publications

Publications from faculty within the Cain Center for Bladder Health help to expand knowledge of bladder health research and improve care for all patients – as well as demonstrate our leadership in this field. Recent publications are listed below.

Dr. Zimmern Clinical Articles Related to Recurrent Urinary Tract Infections (2021 to 2023)

  1. Chavez, Chavez, Kuprasertkul, Carroll, Fuentes, Christie, Alhalabi, Zimmern: Prospective Evaluation of Daily and Weekly Urine PH Variations Along With Diet Intake in Postmenopausal Women with Recurrent Urinary Tract Infections. FPMRS.27:e352-e359, 2021 DOI 10.1097/SPV.0000000000000931 This study discovered two groups of women, those with a urine pH predominantly at or below 6, and a second group with urine pH predominantly above 6 or with variable urine pH trends.
  2. JA Stevens, JA Chavez, AL Chris­tie MS, PE Zimmern M.D. Outpatient elec­trofulguration for antibiotic-recalcitrant recurrent urinary tract infections in women with trigonitis alone. J Urin Trac Infec. 2021 Mar;1(1);101. The best candidates for fulguration are those with lesions limited to the trigone on cystoscopy evaluation. These women tend to fare well long-term although this is not universal. There are failures (<20%) requiring additional therapies.
  3. Kuprasertkul A, Gadhvi J, Fuentes J, Khan F, Neugent M, De Nisco NJ, Zimmern PE. Reduced urothelial expression of uroplakin-IIIa in cystitis areas in bladders of postmenopausal woman with recurrent urinary tract infections: pilot study. World J Urol. 2022 Jun 4. doi: 10.1007/s00345-022-04050-y. Epub ahead of print. PMID: 35665841. This critical study focused on uroplakins, which serve for bacterial attachment to the surface of the bladder before bacteria can enter deep into the tissues and get integrated there forever. Some biopsies were taken after fulguration showing surface remodeling preventing such attachment, thus explaining the lack of cystitis recurrence on prior fulgurated areas observed on cystoscopy.
  4. Ordonez J, Christie AL, Zimmern PE. Role of Flexible Cystoscopy in the Management of Postmenopausal Women with Recurrent Urinary Tract Infections. Urology. 2022 Nov;169:65-69.doi: 10.1016/j.urology.2022.07.040. Epub 2022 Aug 7. PMID: 35944653. This is a very important study which showed that 75% of women evaluated for recurrent urinary tract infections are found with lesions of chronic cystitis embedded in their bladder wall during office cystoscopy.
  5. Ethan Fan, Marjan Dashti, Jorge Fuentes, Larry Reitzer, Alana L. Christie and Philippe E. Zimmern. D-mannosuria Levels Measured 1 h after D-mannose Intake can select out Favorable Responders: A Pilot Study. Neurourol Urodyn. 2022;1-7. https://doi.org/10.1002/nau.25059. When a woman takes an oral dose of D-mannose to treat her urinary tract infection, how much D-mannose ends up in the urine bathing her bladder, where it is supposed to block bacterial attachment by attaching to the bacterial terminal pili site? This study shows that the responders are around 50%. So, how does D-Mannose really work? The clinical data on D-mannose is weak (Cochrane review) and only one randomized study has been published using 2 gm daily over a 6-month period. There is no long-term data published so far.
  6. Ma R, Chavez JA, Christie AL, Zimmern PE. Electro-fulguration for extensive inflammatory bladder lesions in post-menopausal women with antibiotic-recalcitrant recurrent urinary tract infections. Int Urogynecol J. 2022 Sep 27. doi: 10.1007/s00192-022-05360-w. Epub ahead of print. PMID: 36166061. This study explores the role of fulguration in women with chronic cystitis stages 3 and 4. These unfortunate women have a large amount of lesions embedded in their bladder wall and nearly never respond durably to any form of oral antibiotics. Fulguration is at the moment their last resort alternative before considering a surgical removal of their bladder to prevent fatal urosepsis.
  7. Shivani Gaitonde, Alana L. Christie, Priya Garigipati, Feras Alhalabi, Philippe E. Zimmern. Very Long-term Outcomes after Electrofulguration for Antibiotic-Refractory Recurrent Urinary Tract Infections in a Predominantly Menopausal Cohort of Women. Journal of Urology. 210:649-658, 2023 doi.org/10.1097/JU.0000000000003612. This was considered a seminal article by the Journal of Urology. We reported our favorable very long-term experience with fulguration in predominantly menopausal women suffering from recurrent urinary tract infections. Few studies nowadays extend to 10 years or beyond. This is an exciting and reassuring study for our suffering women, and for us as clinicians. The next step is to confirm these findings with a randomized controlled trial.
  8. J.J., Crivelli, P.E.; Zimmern (2020) Vesicular Cystitis: A Chronic Cystitis Variant Often Unresponsive to Antibiotics and Electrofulguration.  Urol Int 2020. doi: 10.1159/000510320 This is the first report on this type of cystitis in women with recurrent urinary tract infections. The most common is cystitis cystica. The presence of these innumerable tiny cysts covering the bladder surface is easily recognizable. Their pathophysiology remains an enigma, as is the best way to treat this condition which leads to frequent recurrences and may end up with bladder removal.
  9. Chavez JA, Christie AL, Zimmern PE. Favorable Outcomes of Repeat Electrofulguration Procedures in Women with Antibiotic-Refractory Recurrent Urinary Tract Infections. Urology. 2020 Dec;146:83-89. Doi: 10.1016/j.urology.2020.08.030. Epub 2020 Aug 29. PMID; 32871138 Repeat electrofulguration can salvage another 20-30% of women with recurrent urinary tract infections, and is an approach frequently adopted in extensive cystitis stages 3 and 4.
  10. Maredia NN, Fanning MJ, Christie AL, Prokesch BC, Zimmern PE: Adverse effects of chronic nitrofurantoin therapy in women with recurrent urinary tract infections in an outpatient setting. World J Urol. 2021 Jul;39(7):2597-2603. doi: 10.1007/s00345-020-03464-w. Epub 2020 Oct 7. PMID: 33026477. Long-term daily low dose nitrofurantoin therapy can be beneficial in reducing recurrent acute and severe episodes of urinary tract infections, but has risks which although very limited can be major if not recognized in a timely fashion.
  11. Carroll TF, Christie AL, Prokesch BC, Zimmern PE. Fosfomycin Prevents Intravenous Antibiotic Therapy in Women With Recurrent Urinary Tract Infections: A Retrospective Review. Female Pelvic Med Reconstr Surg. 2022 Feb 1;28(2):109-114. doi: 10.1097/SPV.0000000000001083. PMID: 35084371. Fosfomycin is first line therapy in Europe but our oral agent of last recourse in the US due to cost and lack of sensitivity testing in standard urine cultures. Our study shows it can save patients and our health system from the higher costs of an intravenous antibiotic course.
  12. Reddy M, Zimmern PE. Efficacy of Antimicrobial Intravesical Treatment for Uncomplicated Recurrent Urinary Tract Infections: A Systematic Review. Int Urogynecol J 33, 1125-1143 (2022). https://doi.org/10.1007/s00192-021-05042-z Intravesical therapy is a logical approach to avoid the side-effects of oral antibiotic treatment. Few agents are available and their efficacy is limited.
  13. Lee C, Chavez JA, Alhalabi F, Christie AL, Zimmern PE.  Evolution of Urinary Tract Infections after Sub-urethral Sling Removal with and without Electrofulguration. J UTI 2021 Nov;1(1):102. DOI 10.31021/JUTI.20211103  Mid-urethral sling can cause obstruction and result in urinary retention which leads to recurrent urinary tract infections. When lesions of chronic cystitis are recognized, this work suggests that concurrent sling release and fulguration of these cystitis lesions can provide durable cure/improvement in those with more advanced stages.
  14. Ethan Fan, Jacqueline A. Chavez, Juliann M. Chavez, Alana L. Christie, Philippe E. Zimmern: Does urinary pH and diet influence the rate of urinary tract infection recurrence after electrofulguration in women with antibiotic-recalcitrant recurrent urinary tract infections? Urology, 2022,  ISSN 0090-4295, This study explores the complex interaction of urine pH and diet in the risk of recurrence after fulguration in women suffering from recurrent urinary tract infections.
  15. Fan EM, Zimmern PE (2022) Challenges of Managing lower Urinary Tract Symptoms in Women with Tamoxifen Use, Women’s Health Report 3:1, 430-436, DOI: 10.1089/whr.2021.0147. Tamoxifen effectively treats breast cancer but can lead to challenging management of women with urinary tract infections, urinary incontinence, and/or pelvic organ prolapse. Our limited experience indicates that our treatment approach should remain the same and can lead to successful outcomes.
  16. Kenee PRM, Christie AL, Zimmern PE. Cranberry Supplement, D-Mannose, and other OTC modalities for Prevention of Recurrent UTI in Women Post-Electrofulguration. Int J Womens Health. 2022 May 3;14:643-653. doi: 10.2147/IJWH.S355469. PMID: 35535150; PMCID: PMC9078870. Non-antibiotic therapies are popular among those suffering from recurrent urinary tract infections.These therapies are poorly understood overall in terms of an ideal candidate, urinary metabolism (responder vs non-responders), and best dosing.
  17. Daniel Le, Wenqing Zhu, Joseph Crivelli, Rosalind Ma, Shan Sun-Mitchell, Christopher Kribs, Philippe Zimmern: Risk factors and Their Impact on Long-Term Outcomes of Women with Antibiotic-Recalcitrant Recurrent Urinary Tract Infections Undergoing Cystoscopy with Fulguration. Intl Journal of Intelligent Technologies and Applied Statistics Vol. 15, No. 1, (2022) 47-61, DOI:10.6148/IJITAS.202203_15(1).0005 This study researched risk factors to predict a successful outcome after a fulguration procedure in the long-term. The study included women at different stages of cystitis, an important variant for durable outcome not fully appreciated at the time that work was done.
  18. Fan EM, Seyan ZJ, Hogins JB, Christie AL, Abreau M, et al. (2022) The Effect of Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors on Urinary Tract Infections. J Clin Diabetes 6: 147. These newer therapies to combat diabetes result in a very high elevation of glucose in urine. Glucose is the favorite food for bacterial growth. Surprisingly, women on these therapies have a low incidence of recurrent urinary tract infections. Does high glucose concentration in urine really protect against a urinary tract infection?
  19. Zimmern PE, Sawant NV, Chang SS, Warner RW, De Nisco NJ. Intravesical VesiX as a Last Resort Therapy in Women With Antibiotic-Refractory Recurrent Urinary Tract Infections Contemplating Bladder Removal: A Preliminary Report. Ann Pharmacother. 2022 Jul 15:10600280221112111. doi: 10.1177/10600280221112111. Epub ahead of print. PMID: 35838251. With FDA approval, this limited study of 3 women destined to have their bladder removed for antibiotic-recalcitrant recurrent urinary tract infections proved that intravesical VesiX could be administered safely. Prior ex vivo studies from Dr DeNisco’s lab indicated a very high and rapid efficacy of VesiX to eliminate both Gram-positive and Gram-negative organisms in urine.
  20. Hogins J, Fan E, Seyan Z, Kusin S, Christie AL, Zimmern PE, Reitzer L. Bacterial Growth of Uropathogenic Escherichia coli in Pooled Urine Is Much Higher than Predicted from the Average Growth in Individual Urine Samples. Microbiol Spectr. 2022 Oct 26;10(5):e0201622. doi: 10.1128/spectrum.02016-22. Epub 2022 Sep 26. PMID: 36154127; PMCID: PMC9603375. Pooled urine has been popular to study bacterial growth. This study shows that this is not a desirable method because pooled urine is not a real patient’s urine. The nutrients found in this pooled urine are unique, thus the study findings will not be reproducible for studies carried out in another lab with a different set of urine doners.
  21. Rivera-Tarazona LK, Sivaperuman Kalairaj M, Corazao T, Javed M, Zimmern PE, Subashchandrabose S, Ware TH. Controlling shape morphing and cell release in engineered living materials. Biomater Adv. 2022 Dec;143:213182. doi: 10.1016/j.bioadv.2022.213182. Epub 2022 Nov 2. PMID: 36375222. Engineered living materials can deliver durable friendly bacteria and/or therapies directly in the bladder with a predictable release system over several days. A large NIH grant funding allowed this preliminary work.
  22. Sam Kusin, Ethan Fan, Bonnie Prokesch, Alana Christie, Philippe Zimmern. Empiric Versus Culture Based Antibiotic Therapy for Suspected UTIs in Menopausal Women.  WJU 2023, https://doi.org/10.1007/s00345-023-04303-4. During COVID-19, late at night or at the end of the week, empiric therapy is sometimes the only option to treat very symptomatic women with recurrent urinary tract infections. There is concern with this approach that the choice of antibiotic is not culture based as recommended by current guidelines. Therefore, unnecessary treatments and use of the wrong antibiotics, along with the risks of antibiotic adverse effects and increased antibiotic resistance are all the negatives which need to be balanced against several days of persistent or worsening urinary tract infection symptomatology with risk of progression to urosepsis or pyelonephritis. Empiric treatment may have a beneficial role but a larger randomized study will be needed to confirm these early findings.
  23. Hogins J, Sudarshan S, Zimmern P, Reitzer L. Facile transduction with P1 phage in Escherichia coli associated with urinary tract infections. J Microbiol Methods. 2023 Apr 8:106722. doi: 10.1016/j.mimet.2023.106722. Epub ahead of print. PMID: 37037272. An important technical improvement to study bacterial growth.
  24. Patel RS, Christie AL, Zimmern PE. Does bacterial motility influence the extent of bladder wall involvement in women with recurrent urinary tract infections? Urol Sci [34:93-8, 2023 DOI 10.4103/UROS.UROS_74_22. One wonders how bladder infections progress from early stages involving the trigone only to the whole bladder being covered with infection sites. Is it a property of the infecting bacteria, a host deficiency, a result of repeated infections, a sign of chronically incomplete bladder emptying, or a combination of factors? This study focused on bacterial motility properties but is an indirect study indicating the presence of more “difficult to treat” bacteria in the more advanced stages.
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