New research

Reassessment of routine midstream culture in diagnosis of urinary tract infection
Sanchutha Sathiananthamoorthy, James Malone-Lee, Kiren Gill, Anna Tymon, Trang K. Nguyen, Shradha Gurung, Linda Collins, Anthony S. Kupelian, Sheela Swamy, Rajvinder Khasriya, David A. Spratt, Jennifer L. Rohn – 2018

Midstream urine culture (MSU) are still widely seen as the gold standard diagnostic test for acute UTIs. But this research published in the Journal of Clinical Microbiology found that MSUs

  • miss a wide variety of bacteria
  • and can’t distinguish between infected patients from normal controls.

Cross over data supporting long term antibiotic treatment in patients with painful lower urinary tract symptoms, pyuria and negative urinalysis 2018

The paper published in the International Urogynecology Journal measured the effects of an unplanned and sudden end to treatment of patients with chronic UTI. Of a group of 221 patients

  • 199 patients reported a deterioration of their condition
  • 11 patients required hospital care.

Recalcitrant chronic bladder pain and recurrent cystitis but negative urinalysis: What should we do?
By Sheela Swamy, William Barcella, Maria De Iorio, Kiren Gill, Rajvinder Khasriya, Anthony S. Kupelian, Jennifer L. Rohn, James Malone-Lee. International Urogynecology Journal, March 2018

This research study looked at how lower urinary tract symptoms may be associated with chronic urinary tract infection undetected by routine diagnostic tests. Antimicrobial therapy might confer benefit for these patients.

A blinded observational cohort study of the microbiological ecology associated with pyuria and overactive bladder symptoms
Kiren Gill, Ryoon Kang, Sanchutha Sathiananthamoorthy, Rajvinder Khasriya, James Malone-Lee

This study supports the need to re-examine the OAB phenotype given this association with microbial colonisation.

Men only studies

The Prevalence and Overlap of Interstitial Cystitis/Bladder Pain Syndrome and Chronic Prostatitis/Chronic Pelvic Pain Syndrome in Men
RAND Interstitial Cystitis Epidemiology Male Study. The Journal of Urology, v. 189, no. 1, Jan. 2013, p. 141-145


Importance of Biofilms in Urinary Tract Infections: New Therapeutic Approaches
By Sara M. Soto.

This paper published in Advances in Biology in 2014 looks specifically at the issue of bacterial forming biofilms within the urinary tract , the difficulty of eradication due to the presence of persistent cells within the urinary epithelium and a review of new therapeutic tools that are necessary. It concludes that new antimicrobial drugs that inhibit bacterial virulence and biofilm formation are needed.

Dr. Bill Costerton: Diagnosing and Treating Biofilm Infections
Awarded the nicknames, ‘Father of Biofilms’ and ‘The King of Slime’, Dr Costerton saw microbial life as a community of microorganisms with the ability to attach to hydrated surfaces. He realized not only the importance of biofilms, but also their uniqueness displayed by microorganisms within biofilms, such as antibiotic tolerance or slow growth rate.
Watch Dr Bill Costerton on YouTube

Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era.
Kostakioti M, Hadjifrangiskou M & Hultgren SJ

Published in Cold Spring Harbour Perspectives in Medicine in April 2013 discusses the various bacterial methods of attachment and then biofilm formation on surfaces and within cells, highlighting several medically important pathogens, and discusses recent advances for new strategies aimed at biofilm prevention and/or dissolution.

Microbial Biofilms in Urinary Tract Infections and Prostatitis- Etiology, Pathogenicity, and Combating strategies
Cristina Delcaru, Ionela Alexandru, Paulina Podgoreanu, Mirela Grosu, Elisabeth Stavropoulos, Mariana Carmen Chifiriuc and Veronica Lazar 2016

Microbial Biofilms in Urinary Tract Infections and Prostatitis: Etiology, Pathogenicity, and Combating strategies
A short paper published December 2016 in Pathogens evaluating the role of microbial biofilms in the development of female UTI and different male prostatitis syndromes, their consequences, as well as the challenges for therapy.

Implication of biofilm formation in the persistence of urinary tract infection caused by uropathogenic Escherichia coli
S.M.Soto, A.Smithson, J.P.Horcajada, J.A.Martinez, J.P.Mensa, J.Vila 2006

Escherichia coli is the most frequent bacteria involved in urinary tract infection. An acute e coli UTI can lead to recurrent infection. In this study, published in Clinical Microbiology and Infection in 2006. E. coli strains causing relapse and re-infection were analysed. The production of biofilm in these e-coli was significantly more frequent among strains causing relapse. It concludes that Biofilm testing may be helpful for patients to help formulate an approach to eradicate persistent biofilm-forming E. coli strains and prevent subsequent relapses.

Biofilm Formation
Published in the International Journal of Health Research and Medical Sciences in 2014

The study observed the ability of urinary pathogens to form biofilms and their antimicrobial resistant patterns. Biofilm forming pathogens showed higher antimicrobial resistance as compared to non-biofilm bacteria. They concluded that urinary pathogens should be routinely screened for biofilm formation.


Absolute and relative accuracy of rapid urine tests
Williams GJ1, Macaskill P, Chan SF, Turner RM, Hodson E, Craig JC

Diagnosis of urinary tract infection in children
Christopher D. Doernaand Susan E. Richardsonb

Prevalence of Asymptomatic Bacteriuria in Hospitalized Patients
Sergio E. Trevino, Jeffrey P. Henderson, Jiami Wu, Candice Cass, and Jonas Marschall

Clinical decision rule to identify febrile young girls at risk for urinary tract infection
Gorelick MH and Shaw KN

Low bacterial counts in infants with urinary tract infection
Hansson S, Brandström P, Jodal U, Larsson P

Pyuria and bacteriuria in urine specimens obtained by catheter from young children with fever
Hoberman A, Wald ER, Reynolds EA, Penchansky L, Charron M

Low bacterial count urinary tract infections in infants and young children
Theodoros A. KanellopoulosPaul J. VassilakosMarinos KantzisAikaterini EllinaFevronia KolonitsiouDimitris A. Papanastasiou

Diagnostic accuracy of urinary biomarkers in infants younger than 3 months with urinary tract infection
Nani Jung, Hye Jin Byun, MD, Jae Hyun Park, MD, Joon Sik Kim, MD, Hae Won Kim, MD, and Ji Yong Ha

Accuracy of clean-catch urine collection in infancy
Ramage IJ, Chapman JP, Hollman AS, Elabassi M, McColl JH, Beattie TJ

Urinary tract infection in infants: the significance of low bacterial count
Swerkersson S, Jodal U, Åhrén C, Sixt R, Stokland E, Hansson S

Use of rapid dipstick tests to exclude urinary tract infection in children
Sharief N, Hameed M, Petts D

Low urinary bacterial counts: do they count?
Tullus K

Study of urinary tract infection and bacteriuria in neonatal sepsis
Samayam P1, Ravi Chander B

To clean or not to clean: effect on contamination rates in midstream urine collections in toilet-trained children
Vaillancourt S1, McGillivray D, Zhang X, Kramer MS

The Uriscreen test was not better than standard urinalysis and dipstick tests for detecting urinary tract infection in children
Robert S Wigton, MD, MS

Urinary microbiome

The New World of the Urinary Microbiome in Women
Linda Brubaker and Alan J Wolfe

Published in The American Journal of Obstetrics and Gynaecology in 2015, this paper highlights the inadequacies of the current tools for urinary bacterial testing, outlines new options, details the current interpretation of testing results, and proposes potential clinical uses and relevance. Given the advances in urinary microbial testing, the paper argues this will benefit better understanding of the UM and the bladder, in turn this has significant potential to improve patient treatment.

Biofilm Formartion and Antimicrobial Resistance Pattern Among Uropathogens
CharanKaur Dardi & Sanjivani Maral

Culturing of female bladder bacteria – Nature Communications 2018
Krystal Thomas-White, Samuel C. Forster, Nitin Kumar, Michelle Van Kuiken, Catherine Putonti, Mark D. Stares, Evann E. Hilt, Travis K. Price,Alan J. Wolfe & Trevor D. Lawley 2018

Using a detailed genomic and functional analysis of the bladder microbiota to the gastrointestinal and vaginal microbiotas revealed similar vaginal and bladder microbiota, that are distinct from those observed in the gastrointestinal microbiota.B acterial strains isolated from the vagina and bladder in the same women identified highly similar Escherichia coli, Streptococcus anginosus, Lactobacillus iners, and Lactobacillus crispatus. This suggests an interlinked female urogenital microbiota that is not only limited to disease causing bacteria but also characteristic of normal health-associated commensals.

A case control study examining the bladder microbiome
Natasha Curtiss, Aswini Balachandrana, Louise Krskab, Claire Peppiatt-Wildmanb, Scott Wildmanb, Jonathan Ducketta
The European Journal of Obstetrics Gynaecology and Reproductive Biology 2017
This study aimed to characterise the microbiome in women with no bladder symptoms in comparison to the bladder microbiome in patients with overactive bladder syndrome (OAB). They concluded that the female human bladder has a diverse microbiome noting significant differences between bacterial species present in OAB patients and controls.

Does the Urinary Microbiome Play a Role in Urgency Urinary Incontinence and Its Severity
Frontiers in Cellular & Infection Microbiology 2016
Lisa Karstens , Mark Asquith, Sean Davin, Patrick Stauffer, Damien Fair W.Thomas Gregory, JamesT.Rosenbaum, Shannon K.McWeeney and Rahel Nardos

A pilot study aiming to establish how the urinary microbiome is different between women with and without Urinary Urge Incontinence. They also sought to identify if characteristics of the urinary microbiome are associated with UUI severity. The results demonstrated that the urinary microbiome may play an important role in the pathophysiology of UUI and that loss of microbial diversity may be associated with the severity of patient symptoms.

Gram-Positive Uropathogens, Polymicrobial Urinary Tract Infection, and the Emerging Microbiota of the Urinary Tract
American Society for Microbiology 2016
Kimberly A. Kline and Amanda L. Lewis

The paper reviews the most common uropathogens: Staphylococcus, Enterococcus, and Streptococcus, reviews the issues around polymicrobial urinary tract infection and it’s significance for urine culture. It notes the potential under-reporting of fastidious organisms and atypical Gram-positives as causes of urinary tract infection. Finally, the authors summarize the current research literature discussing the urobiome and discuss the potential role of urogenital microbiota in UTI susceptibility.

Microbial metagenome of urinary tract infection
Ahmed Moustafa, Harinder Singh, Weizhong Li, Kelvin J. Moncera, Manolito G. Torralba, Yanbao Yu, Oriol Manuel, William Biggs, J. Craig Venter, Karen E. Nelson, Rembert Pieper, Amalio Telenti

Published in Scientific Reports in 2018, this study, using genomic analysis from patients, found cases of infection with potential pathogens often missed during routine urine culture due to bacterial species specific growth requirements. They note that conventional microbiological methods are inadequate to identify a large diversity of microbial species that are present in urine, newer genomic testing seems to more comprehensively and quantitatively describe the urinary microbiome.

The Urinary Microbiome and its Contribution to LUTS
Urology and Urodynamics 2017
Marcus J. Drake, Nicola Morris, Apostolos Apostolidis, Mohammad S. Rahnama and Julian R. Marchesi

The International Consultation on Incontinence Research Society (ICI-RS) established a literature review and expert consensus discussion focusing on the increasing awareness of the urinary microbiome, and potential research priorities. Focus was given to differing bacteria interpretation levels in laboratory and the direction of testing towards known UTI causing pathogens. This selective culture compared to newer metogenomic RNA sequencing highlights the possibility that protective or harmful bacteria may be overlooked where microbiological methods are selective. Also reviewed was the potential relationship between a patient’s microbiome and lower urinary tract dysfunction, whether low-count levels of bacterial infections may be clinically significant and mechanisms which could associate micro-organisms with lower urinary tract symptoms.

Questions and challenges associated with studying the microbiome of the urinary tract
Annals of translational medicine
Yige Bao, Kait F. Al, Ryan M. Chanyi, Samantha Whiteside, Malcom Dewar1, Hassan Razvi1, Gregor Reid, Jeremy P. Burton

This paper highlights the opportunities for urinary microbiome investigations and the experiences of the researchers in working with these low abundance samples in the urinary tract. They conclude that learning about the microbiome’s role in urology and disease is in its infancy. There are few longitudinal studies and more are required to understand the urinary microbiome’s development and its influence on health and disease from birth to death. A greater understanding of the role the microbiome play will lead to the modulation of the improvement of health outcomes

The Urinary Microbiota: A Paradigm Shift for Bladder Disorders?
Linda Brubaker, MD, MS and Alan Wolfe, PhD

The study reviews and notes that now that Improved techniques for microbial detection are available, study of the FUM may show an impact on common lower urinary tract disorders, such as urinary incontinence and urinary tract infection. By making refinements to it may be possible to describe the FUM of healthy states, as well as the spectrum of vulnerable, dysbiotic microbial communities that may predispose women to lower urinary tract disorders.

Intracellular bacterial communities

Intracellular lifestyles and immune evasion strategies of uropathogenic Escherichia coli.
By Hunstad DA & Justice SS

Intracellular Bacterial Communities: A Potential Etiology for Chronic Lower Urinary Tract Symptoms.
By Scott, Haake, Churchill, Justice & Kim

Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection
By David A Rosen, Thomas M Hooton,Walter E Stamm, Peter A Humphrey & Scott J Hultgren

Detection of intracellular bacterial communities in a child with Escherichia coli recurrent urinary tract infections.
By Luciana Robino, Paola Scavone, Lucia Araujo, Gabriela Algorta, Pablo Zunino & Rafael Vignoli

Host subversion by formation of intracellular bacterial communities in the urinary tract
Gregory G. Anderson, Steven M. Martin, Scott J. Hultgren 2004

Intracellular Bacterial Communities: A Potential Etiology for Chronic Lower Urinary Tract Symptoms
Ine Jorgensen, Patrick C. Seed 2012

UTI testing

Detecting clinically relevant microrganims we can do better
Paul C. Schreckenberger, Travis K. Price, Evann E. Hilt, Tanaka Dune, Cynthia Brincat, Linda Brubaker, Elizabeth R. Mueller, Alan J. Wolfe 2015

Detecting uropathogens in a urogynaecologic population: a comparison of UTI diagnostic thresholds
Price T, Hilt E, Dune T, Brincat C, Brubaker L, Mueller E, Schreckenberger P, Wolfe A – The International Continence Society 2017

The Problems affecting the diagnosis of urinary tract infection
Temenuga Dacheva & James Malone-Lee 2010

Urine is Not Sterile Use of Enhanced Urine Culture Techniques to Detect Resident Bacterial Flora in the Adult Female Bladder
Evann E. Hilt, Kathleen McKinley, Meghan M. Pearce, Amy B. Rosenfeld, Michael J. Zilliox, Elizabeth R. Mueller, Linda Brubaker, Xiaowu Gai, Alan J. Wolfe, Paul C. Schreckenberger 2014

Urine trouble: should we think differently about UTI?
K. Price & Evann E. Hilt & Tanaka J. Dune & Elizabeth R. Mueller & Alan J. Wolfe & Linda Brusker 2017

Women with symptoms of UTI but negative Urine test
Journal of Microbiology 2017— S Heytens, A De Sutter, L Coorevits, P Cools, J Buelens, L Van Simaey, T Christiaens, M Vaneechoutte, G Claeys 2017


Epidemiology of urinary tract infections: incidence, morbidity, and economic costs
Am J Med. 2002; 113:5–11S

The epidemiology of urinary tract infection
Foxman B1. Nat Rev Urol. 2010 Dec;7(12):653-60. doi: 10.1038/nrurol.2010.190

Diagnosis of coliform infection in acutely dysuric women
Stamm WE, Counts GW, Running KR, Fihn S, Turck M, Holmes KK.
N Engl J Med. 1982 Aug 19;307(8):463-8.

Common errors in diagnosis and management of urinary tract infection
Martina Franz & Walter H Horl.
Nephrology Dialysis Transplantation, Volume 14, Issue 11, 1 November 1999, Pages 2746–2753

Bacteria in the bladder wall of women with lower urinary tract symptoms: An interesting finding
By Vijaya G, Dutta S, Singh A U, Bray R, Digesu A, Fernando R, Khullar V.

Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses
By Mulvey MA, Schilling JD, Martinez JJ & Hultgren SJ

Discrediting microscopic pyuria and leucocyte esterase as diagnostic surrogates for infection in patients with lower urinary tract symptoms: results from a clinical and laboratory evaluation
Kupelian AS, Horsley H, Khasriya R, Amussah RT, Badiani R, Courtney AM, Chandhyoke NS, Riaz U, Savlani K, Moledina M, Montes S, O’Connor D, Visavadia R, Kelsey M, Rohn JL, Malone-Lee J.

The unexplored relationship between urinary tract infections and the autonomic nervous system
By Hibbing, Conover & Hultgren

Urinary tract infections: epidemiology, mechanisms of infection and treatment options.
By Flores-Mireles, Walker, Caparon & Hultgren

From physiology to pharmacy: developments in the pathogenesis and treatment of recurrent urinary tract infections
By Silverman JA, Schreiber HL, Hooton TM & Hultgren SJ

Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection
By Hannan TJ, Totsika M, Mansfield KJ, Moore KH, Schembri MA & Hultgren SJ

Enterococcus faecalis Subverts and Invades the Host Urothelium in Patients with Chronic Urinary Tract Infection
By Harry Horsley, James Malone-Lee, David Holland, Madeleine Tuz, Andrew Hibbert, Michael Kelsey, Anthony Kupelian & Jennifer L. Rohn

Urine trouble: should we think differently about UTI?
K. Price & Evann E. Hilt & Tanaka J. Dune & Elizabeth R. Mueller & Alan J. Wolfe & Linda Brusker 2017

Women with symptoms of UTI but negative urine test Journal of Microbiology 2017
S Heytens, A De Sutter, L Coorevits, P Cools, J Buelens, L Van Simaey, T Christiaens, M Vaneechoutte, G Claeys 2017

The Clinical Urine Culture: Enhanced Techniques Improve Detection of Clinically Relevant Microorganisms
Travis K. Price, Tanaka Dune, Evann E. Hilt, Krystal J. Thomas-White, Stephanie Kliethermes, Cynthia Brincat, Linda Brubaker, Alan J. Wolfe, Elizabeth R. Mueller, Paul C. Schreckenberger