The Role Bacteria Biofilm Have in Identifying, Classifying and Defining UTI in Laboratory and Clinical Screenings of NB Patients That Use CIC in Clinical Settings

1. Running head: THE ROLE BACTERIA BIOFILM...... 1
Dr. Obumneke Amadi-Onuoha_Scripts
The Role Bacteria Biofilm Have in Identifying, Classifying and Defining UTI in Laboratory and
Clinical Screenings of NB Patients That Use CIC in Clinical Settings
By Obumneke Amadi, Dr.PH, MPH, MSHS
Clinical Investigation_CRA_CTR
Review of Literature Draft: 10/1/2018
Introduction
The purpose of this paper review is to write a brief report of the above process that is
used to 1) Define the problem being addressed and its importance, 2) Provide a brief overview of
the science as described in the published literature, 3) Discuss the gaps in knowledge or other
barriers to advancing the science in this area, and 4) Introduce key points and elucidate complex
concepts (that you plan to expand upon in your specific aims or another section of your
proposal). The synthesized and analyzed information provided in the literature review will serve
as the base to transition to the section 2 of the research study.
Literature Search Strategy
The key themes central to the literature review includes defining Urinary Tract Infection
(UTI), Neurologic Bladder Patients (NB) and Clean Intermittent Catheterized, Defining UTI.
Moreover, diverse search terms were used to find and collect broad references from databases
with pdf full text on websites. The search themes include defining UTI, UTI criteria in NB
Patients, diagnosing UTI in Clean Intermittent Catheterized. The primary databases used for
literature search include Google Scholar, PubMed, science direct, Biomedical Central,
Biomedical Journal, and ProQuest. The reason for the choice of databases is because there are
many related articles of the problem observed and they are used to provide evidence for this
study. The terms searched thorough web-based generated sources were drawn from international
journal of pharmaceutical sciences and research, international journal of pharmaceutical sciences
and research, International Journal of Current Microbiology and Applied Science, BJU
international, and others.
The articles and journals that I selected for the literature review were from the year 2010
to present and written in English. In this section 1 review, I will present the review of variations
to adequately define UTI in NB patients using clean intermittent catheterization, an overview of
the science as described in the published literature, gaps to date on the issue and how this study
will promote knowledge to help close the gaps.
Variations in Defining UTIs in NB Patients / Importance
There is a high incidence of UTI in patients with NB (Vigil & Hickling, 2016, p.72) that
are resulting in major morbidity and health care use. Numerous established risk factors exist in
this population; however, others require continuing analysis. The diagnosis of UTI remains
complex, proper urine collection is vital, however, “UTI cannot be diagnosed based on urinalysis

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or clinical presentation alone” (Vigil & Hickling, 2016, p.72). It is important for care providers
to have a good understanding of the different structural risk factors associated with the infection
to enable proper control of its spread or recurrence, such that, they may be modified when
possible.
According to the literature I reviewed, the gaps I identified are revealing that off all the
commonly used measures used to define criteria for urinary tract infection (UTI) in neurologic
bladder (NB) population, that include symptoms, urine culture, there are variations to adequately
define UTI in this population. Research reveals that CIC most used for treatment, in this case,
have a high level of complication in UTI. However, bacterial biofilms play an important role in
UTIs, they are responsible for persistent infections leading to recurrences and relapses.
“according to National Institutes of Health (NIH) about 65% of all microbial infections, and 80%
of all chronic infections are associated with biofilms” (Jamal, Tasneem, Hussain & Andleeb,
2015). The articles suggest that using bacterial biofilm phenotyping may help to understand the
uropathogens, bacterial cofactors in the pathogenesis and epidemiology of UTI in classifying of
UTIs (Wyndaele, Brauner, Geerlings, Bela, Peter & Bjerklund‐ Johanson, 2012). Prasad,
Sharma & Shlini (2018), conducted a study aimed at isolation and characterization of biofilm
forming bacteria from UTI infected patients, using the phenotyping biomarker (bacteria biofilm)
diagnostic methods that include Congo red agar method, microtiter plate assay, and microscopic
examination of the biofilm. The outcome showed that Uropathogenic Escherichia coli (UPEC)
isolates have a strong biofilm forming abilities (pp.1-9). Sonkusale & Tale (2015), examined
the isolation and characterization of biofilm forming bacteria from oral microflora, the result
characterized three strong, two moderate and four weak biofilm forming bacteria (pp.1-10). The
authors of both studies have displayed how Biofilm assay can isolate microorganism strains.
Overview of the science – Diagnostic technologies to Define UTIs in NB Population
Clinicians routine diagnostic and identification of UTI are based on clinical symptoms, that
testing for nitrites and leukocyte esterase, which detect bacteriuria and pyuria, accompanied by a
standardized readout and microscopic urinalysis in the clinical laboratory. In clinical
microbiology laboratory, urine is cultured for pathogenic identification on agar plates for growth,
concentration and isolation. E.g. “voided urine samples that grow ≥104 cfu/ml of a single or
predominant species of uropathogenic bacteria are considered culture positive” (Davenport et al.,
2017, p. 4). Also, chromogenic agar urine cultures enable direct identification of E. coli,
Enterococcus species, and others after incubation, but, isolated bacteria: Enterobacteriaceae
requires further phenotypic characterization (Davenport et al., 2017, pp. 4-5). Others are
automated biochemical detection and mass spectrometry tests, see Table 1- approved
technologies for pathogen detection (Davenport, et., 2017).
Accurate, and on time determination of Uropathogens are integral to the management of
UTIs. Several diagnostic measures are fast and capable of testing, but lack uniformity and
accuracy in diagnostic results e.g. “conducting a urine culture pathogen test takes 2–3 days and
requires a clinical laboratory confirmation”. However, advanced diagnostic measures with
increase speed and accuracy for pathogens identification are available and approved for use in
clinical laboratories for urine cultures. Although these technologies are advance and reduce the
time for diagnosis, yet they do not provide a thorough evidential characteristics of the pathogens.
Some emerging diagnostic urine analysis technologies that include: biosensors, microfluidics,
and others are anticipated to improve UTI diagnosis for direct pathogen detection from urine
samples, and point-of-care testing (Davenport, et al., 2017, p.1).

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In the clinical microbiology laboratory, “urine analysis is performed with automated
systems, and urine collection to pathogen identification takes 18–30 hours commonly”
(Davenport, et al., 2017). Approved technologies for pathogen detection see FIG. 1 in the
appendix. The evidence in this article are convincing, the authors, recognized the development
and implementation of these technologies has the potential to advance accuracy in diagnostic
medicine towards a profound improvement in patient care and public health.
Gaps in Knowledge or Other Barriers to Advancing the Science in This Area
Lugtenberg, Burgers,Zegers-van Schaick, & Westert (2010), examined the barriers to the
implementation of a guideline on UTI perceived by Dutch general practitioners (GPs) and to
explore interventions to overcome these barriers. The authors explained there is the availability
of evidence-based guidelines on UTI, but for an unexplained reason, the adherence to these
guidelines have wide variations among clinicians. The UTI guideline developed by the Dutch
College of General Practitioners (NHG), defined UTI as a positive nitrite test or a dipslide with
at least 104 colony-forming units per ml urine (p.2). Lugtenberg, Burgers,Zegers-van Schaick,
& Westert (2010), revealed that one of the perceived barriers to diagnosing UTI was a lack of
agreement with the guideline recommendation and lack of inconvenient resources/materials.
They authors suggested, small group education to raise awareness of the supporting evidence of
guideline recommendations for UTI diagnosing (p.3).
Bates (2013), discussed UTI as one of the most commonly diagnosed infections in both
outpatient and inpatient populations. The author explained that it is important for clinicians to
understand the values and limitations of urinalysis and urine culture, to make an accurate
diagnosis and analysis. Bates (2013), revealed that understanding of the significance of test
characteristics and the incorporation of patient symptoms may be a barrier to clear defining of
UTI. The author concluded that clinical interpretation of urinalysis and urine culture results
requires careful review of symptoms and test characteristics (para.18).
Key Points and Elucidate Complex Concepts
What is not known is the effective measure to evidently (clearly) define UTIs in NB
patients using clean intermittent catheterization (CIC) due to variations in its definitions from the
common standards, symptomatology, urine culture and microbiological methods for diagnosing
UTIs. Therefore, it is important to clearly understand what role phenotyping does biomarker
(bacteria biofilm) diagnostic measure have in identifying, classifying and defining UTI in
laboratory and clinical screenings of NB patients that use CIC in clinical settings, and how
effective would its application be to evidently (clearly) identify, classify and define UTIs in
laboratory and clinical screenings of NB patients that use CIC in clinical settings.
Further evidence to support the study will be in section 2 that includes, knowledge on
research to date on the issue; UTIs definition and criteria’s and types of diagnostic measures to
provide a thorough understanding of the nature of the problem. Another suggested perception
maybe to understand the the ease of accessibility of the device focused on the cost of obtaining
the device to work in clinical laboratories.
In the third section of this paper, I will present an assessment of the suggested diagnostic
evidence bacteria biofilm, to examine what role it may have in identifying, classifying and
defining UTI in laboratory and clinical screenings of NB patients that use CIC in clinical settings
in the population of interest that would function as a foundation for summarizing the research
problem and purpose.
Summary

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Observing the evidential diagnostic mechanism towards proper UTIs identification and
definition in NB patients and the general UTI population in clinical is a complicated and consists
of variable definitions. This study will help advance knowledge in the role new and advance
clinical diagnostic measures used in UTI diagnosis have, to clearly identify pathogens that cause
UTIs and define UTIs in NB patients and other patients that have UTIs. The study will also help
to promote awareness of the guidelines and new diagnostic technologies that may delver an
effective and evident classification and defining of UTIs for clinicians. The literatures’ have
illustrated, the attribution of the cause for the variation in defining UTIs. Identifying the
diagnostic measure that would effectively help to diagnose and define UTIs for treatment
improvement have given a good understanding of what is required to improve patient care
practice by clinicians, practitioners and other health professionals.

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References
Bates, B. N. (2013). Interpretation of urinalysis and urine culture for UTI treatment. US
Pharm, 38(11), 65-68
Davenport, M., Mach, K. E., Dairiki Shortliffe, L. M., Banaei, N., Wang, T.-H., & Liao, J. C.
(2017). New and developing diagnostic technologies for urinary tract infections. Nature
Reviews. Urology, 14(5), 296–310. http://doi.org/10.1038/nrurol.2017.20
Jamal, M., Tasneem, U., Hussain, T., & Andleeb, S. (2015). Bacterial biofilm: its composition,
formation and role in human infections. RRJMB, 4(3), 1-15.
Lugtenberg, M., Burgers, J. S., Zegers-van Schaick, J. M., & Westert, G. P. (2010). Guidelines
on uncomplicated urinary tract infections are difficult to follow: perceived barriers and
suggested interventions. BMC family practice, 11(1), 51.
Prasad, P. K., Sharma, P., & Shlini, P. (2018). Isolation and characterization of biofilm
forming bacteria from urinary tract infected patients. international journal of
pharmaceutical sciences and research, 9(5), 1886-1894.
Sonkusale, K. D., & Tale, V. S. (2015). Isolation and characterization of biofilm forming
bacteria from oral microflora. International Journal of Current Microbiology and
Applied Science, 2, 118-127.
Vigil, H. R., & Hickling, D. R. (2016). Urinary tract infection in the neurogenic
bladder. Translational Andrology and Urology, 5(1), 72–87.
http://doi.org/10.3978/j.issn.2223-4683.2016.01.06
Wyndaele, J. J., Brauner, A., Geerlings, S. E., Bela, K., Peter, T., & Bjerklund‐ Johanson, T. E.
(2012). Clean intermittent catheterization and urinary tract infection: review and guide
for future research. BJU international, 110(11c), E910-E917

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Appendix
Table 1:
Approved technologies for pathogen detection
Technology Commercial assay AST Advantages Disadvantages Refs
Nitrite and
leukocyte
esterase
Dipstick (lateral flow
assay)
No Point of care Poor
specificity
29
Conventional
culture
 VITEK
 MicroScan
Yes Standard of
care,
sensitive,
and
inexpensive
Time
consuming, not
translatable to
point-of-care
applications
25,26
Urinalysis and
microscopy
 sediMAx
 CLINITEK
Atlas
 Sysmex UF-
1000i
 Iris iQ200
No Fast, detects
the presence
of bacteria
No pathogen
identification
32–34
MALDI-TOF
mass
spectrometry
 VITEK MS
 Bruker
MALDI-TOF
Under
development
Fast,
sensitive,
specific,
potential for
simultaneous
AST
detection
Expensive for
initial
equipment
49–54

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Technology Commercial assay AST Advantages Disadvantages Refs
Fluorescent in
situhybridization
(FISH)
AdvanDx QuickFISH Under
development
Rapid
detection,
high
sensitivity
and
specificity
Requires
multiple
probes for all
possible
urinary
pathogens
61–63
Microfluidics UTI Biosensor Assay
(not FDA approved)
Under
development
Integrated
platform,
rapid
detection
direct-from-
patient
samples,
small
footprint
System is not
fully
automated,
poor data from
low
concentration
of bacteria
82,83, 94,95
PCR (clinical
isolates)
 GeneXpert
 SeptiFast
 FilmArray
Resistance-
gene probes
available
Specific,
sensitive,
and rapid
Requires
multiple
probes for all
possible
urinary
pathogens and
extensive
initial
processing
68–73
Immunological-
based assays
RapidBac No Rapid and
inexpensive
Poor
specificity and
sensitivity
31

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Technology Commercial assay AST Advantages Disadvantages Refs
Forward light
scattering
 Uro-Quick
 BacterioScan
Under
development
Inexpensive
potential for
AST
No species
indentification
40,41
AST, antimicrobial susceptibility testing; MALDI-TOF, matrix-assisted laser desorption
ionization–time of flight; MS, mass spectrometry.