Long-term antibiotics prevent urinary tract infections in the elderly

Running head: INDEPENDENT STUDY
To what degree do long term antibiotics prevent the recurrence of urinary tract infections in
the elderly?
Name of the Student
Name of the University
Author Note

1INDEPENDENT STUDY
Abstract
Background- Urinary tract infections (UTI) refer to infections that affect the urinary system,
including the urethra and urinary bladder. Older adults face this infection more often, when
compared to their younger counterparts.
Objective- To determine the extent by which long-term antibiotics reduce the risks of relapse
of UTI in older adults.
Methodology- A systematic review has been conducted by searching the three electronic
databases PMC, CINAHL, and MEDLINE. Google scholar search engine was also used for
retrieving articles with the use of key terms that were combined with boolean operators.
Articles published in English, from 2010, till date were extracted. The GRADE approach was
used for determining the quality of evidences reported in the article.
Results- Nine articles were included in data analysis that resulted in the identification of
three research themes namely, (i) most effective antibiotics, (ii) extent of reduction of UTI,
and (iii) antimicrobial resistance.
Conclusions- There were variations in the results reported by researchers, in relation to the
impacts of long-term antibiotic prophylaxis on UTI relapse management. Further research
should involve meta-analysis and due emphasis must also be placed on assessing the effects
of non-pharmacological interventions.
Keywords: urinary tract infection, UTI, older, antibiotics, long-term, effect, relapse

2INDEPENDENT STUDY
Table of Contents
Chapter 1: Introduction..............................................................................................................4
Problem statement..................................................................................................................4
Research question...................................................................................................................6
Research aim..........................................................................................................................7
Research objectives................................................................................................................7
Chapter 2: Literature review......................................................................................................8
Definition and Uses................................................................................................................8
Search strategy.......................................................................................................................8
Key terms...............................................................................................................................9
Inclusion and exclusion criteria...........................................................................................10
Literature review results.......................................................................................................11
Chapter 3: Methodology..........................................................................................................30
Research methodological approaches..................................................................................30
Inductive reasoning..............................................................................................................31
Research paradigm...............................................................................................................32
Data collection.....................................................................................................................34
Data analysis........................................................................................................................35
Chapter 4: Results....................................................................................................................38
Most effective antibiotics.....................................................................................................38
Extent of reduction of UTI...................................................................................................40
Antimicrobial resistance.......................................................................................................42

3INDEPENDENT STUDY
Chapter 5: Discussion..............................................................................................................44
Overall discussion................................................................................................................44
Chapter 6: Conclusion..............................................................................................................50
Recommendations................................................................................................................52
References................................................................................................................................54

4INDEPENDENT STUDY
Chapter 1: Introduction
Also referred to as antibacterials, antibiotics are medications that have the capability
of destroying or slowing down the growth and proliferation of bacteria. In other words, these
encompass several powerful drugs that are used for the treatment of bacterial diseases, and
are particularly ineffective against viral infections like cough, cold, and flu (Spellberg,
Bartlett and Gilbert 2013). The fruitful consequence of antimicrobial therapy that comprise of
antibacterial compounds primarily depends on a plethora of factors such as, defence
mechanism of host, the site of infection, and the pharmacodynamics and/or pharmacokinetic
properties of the antibacterial agent (Cotter, Ross and Hill 2013). According to Flores-
Mireles et al. (2015) urinary tract infections (UTIs) occur more in the elderly, due to bacteria
invasion. However, they might also be a consequence of infection due to some kind of fungi.
The elderly people are commonly prescribed antibiotics for alleviating the classic symptoms
of UTI that commonly comprise of frequent urination, burning pain, bloody and cloudy urine,
pelvic pain among women, and urine having a strong odour (Hooton 2012). This systematic
review will explore the impacts of long-term antibiotic usage in the elderly population,
suffering from UTI.
Problem statement
The widespread prevalence of UTI among the elderly can be supported by results
from a study where an estimated 16.55% elderly women reported presence of UTI, with
Escheria coli being responsible for the infections in 76.56% of the cases, Furthermore, an
estimated 34.69% and 21.42% were also found resistant to trimethoprim-sulfamethoxazole
and fluoroquinolones, respectively (Marques et al. 2012). The prevalence of UTI in the older
population was also elucidated by Mirsaidov and Wagenlehner (2016) who identified the
challenges faced by physicians in treating asymptomatic bacteriuria in long-term care
facilities, such as, prostate enlargement, overactive bladder, and indwelling bladder

5INDEPENDENT STUDY
catheters. Absence of standards have also been correlated with an increase in antibiotic
selection pressure that results in the origin of multidrug-resistant organisms. Rowe and
Juthani-Mehta (2014) also opined that recognising which patients need antibiotic
management of symptomatic UTI is thought-provoking. Under such circumstances, clinicians
often select treatment modalities with empiric antibiotics, which in turn results in overdo of
antimicrobials, and leads to the manifestation of increased rates of bacterial resistance. The
International Clinical Practice Guidelines projected by the IDSA and the European Society
for Microbiology and Infectious Diseases recommend the administration of 100mg
nitrofurantoin monohydrate/macrocrystals, twice, for consecutive five days, and also
encourage the administration of 160/800 mg TMP/SMX, for three days, twice daily.
Taking into consideration the over-diagnosis of UTI among older people, antibiotic
prophylaxis might essentially be approved for indications that characterise restricted vaginal
symptoms or bladder dysfunction, rather than real UTI, and therefore will not confer the
proposed advantage (Marschall et al. 2013). Further evidences from research reports suggest
that UTIs contribute to as much as 15.5% of the total infectious disease hospitalisations that
occur in older adults, aged beyond 65 years, and are second to pneumonia. Owing to the fact
that UTIs are largely responsible for roughly 6.2% deaths due to infectious diseases, true UTI
diagnosis remains controversial among the principal healthcare providers (Detweiler, Mayers
and Fletcher 2015). The researchers also illustrated that there are numerous studies that have
failed to demonstrate any mortality or morbidity benefits to antibiotic therapy, in either long-
term care facility or community-dwelling residents with UTI.
Frailty, multimorbidity, and polypharmacy have been identified to be more
widespread in older adults and act in the form of contributory factors for possible harms such
as, those connected to drug interactions (Herr et al. 2015). Compton (2013) stated that usage
of more than five or equivalent medications in the geriatric population predisposes them to

6INDEPENDENT STUDY
increased risks of falls, and drug associated cognitive changes that alter their health status.
Comorbidities related with UTI in older adults also comprise of stroke, Parkinson’s disease,
diabetes, dementia, which in turn increases their length of hospitalisation and brings about a
deterioration in the overall quality of life of the elderly (Genao and Buhr 2012). Continuous
antibiotic prophylaxis (CAP) is typically recommended for the effective prevention and
management of UTI. Results from a systematic review suggested that children who reported
high-grade HN and received CAP manifested a meaningfully lesser rate of UTI, in
comparison to their counterparts who had not been administered CAP, thus demonstrating the
overall levels of efficacy of CAP in UTI prevention (Braga et al. 2013).
Results from another systematic review conducted by Williams and Craig (2011) also
suggested that although antibiotic therapy failed to lower the risks of symptomatic UTI
among children, upon assessing their impacts in trials that demonstrated low bias risks, a
statistically noteworthy reduction was observed in the symptoms (RR 0.68, 95% CI 0.48 to
0.95). Reports from the systematic review also highlighted that nitrofurantoin had
suggestively lesser risk of resistance, when compared to cotrimoxazole (RR 0.54, 95% CI
0.31 to 0.92) (Williams and Craig 2011). There also exist several significant clinical
uncertainties involving long-term antibiotic administration in older adults who report
recurrent UTI, together with consequence on frequency of infective incidents, optimal period
of prophylaxis, contrary effects, danger of relapse succeeding cessation of prophylaxis, and
outcome on urinary antibiotic resistance. Therefore, this systematic review aims to review
scholarly pieces of evidences that have already been conducted before, in order to compare
the extent and degree to which long-term antibiotic prophylaxis prevent the recurrent of UTI
in geriatric population, when compared to non-antibiotic therapy or placebo.

7INDEPENDENT STUDY
Research question
To what degree do long term antibiotics prevent the recurrence of urinary tract
infections in the elderly?
The aforementioned research question was categorised into the core four elements of
the PICO framework, with the aim of creating a succinct and concise search strategy for
extraction of literature. The table given below denotes the components of the framework, in
relation to the research question:
PICO components Research question components
P/Population Older adults (>60 years) having urinary
tract infections
I/Intervention Long-term antibiotic therapy
C/Comparison Placebo or non-antibiotic therapy
O/Outcomes Extent of impact
Table 1- PICO components
Research aim
To investigate the degree do long-term antibiotics avert the recurrence of urinary tract
infections (UTIs) in the elderly.
Research objectives
 To determine the effects of long-term antibiotics on elderly patients having recurrent
UTI
 To explore the adverse events that are commonly reported during long-term
antibiotics on elderly patients having recurrent UTI
 To determine the impacts of long-term antibiotics on bacterial resistance

8INDEPENDENT STUDY
Hence, the chief objective of this systematic review is to collect data, critically appraise
them, and qualitatively synthesise the findings for obtaining an exhaustive summary on the
benefits and problems of long-term antibiotic prophylaxis for older adults, in order to better
inform clinicians and patients, at the time of clinical decision making.

9INDEPENDENT STUDY
Chapter 2: Literature review
The major aim of this second chapter is to provide a comprehensive structural and
theoretical review of pieces of scholarly evidences that have been previously published, are
closely associated and pertinent to the research question. The literature review was
accomplished by conducting a thorough identification, exploration, and discussion of
information that was available, while illustrating the implication of applicable research and
recognising gaps in current knowledge. The chapter begins with a clear definition of literature
review and the associated objectives, succeeded by facts of the literature search policy,
exclusion and inclusion criteria and process of review.
Definition and Uses
Literature reviews are typically described in the form of comprehensive studies that
involve interpretation of scientific literature, associated to a phenomenon that is being
investigated. Literature reviews are imperative in influencing several stages of a research
investigation (both quantitative and qualitative) (Machi and McEvoy 2016). While literature
reviews that involve qualitative articles help in placing relevant findings of scientific
investigations, within context of knowledge that has already been acquired, those
encompassing quantitative articles are employed for stating the purpose of research,
suggesting a theoretical framework, and summarising relevant numerical information on the
research topic.
Search strategy
The literature review involved conduction of a computerised search for scientific
literature, which was determined by the research aims, research question, and objectives. The
literature review focused on collection of information from applicable published works,
counting in peer-reviewed journals and professional-body publications. Supplementary

10INDEPENDENT STUDY
searches were also conducted for inclusion of ‘grey’ literature sources that were produced in
printed and/or electronic format by government, academic, industry, and business
organisations. The search strategy also encompassed the use of snowball technique, whereby
the bibliography and references lists from related journals were examined to recognise
supplementary significant literature. Literature explorations were executed and updated
continually at various phases of the research, in order to apprise the literature. The literature
was searched from three electronic medical databases that were suggested by the university
library services and Aveyard for researchers and students who undertook investigation
connected to health and medicine (Aveyard 2014). The searched databases and search
engines included:
 Cumulative Index of Nursing and Allied Health Literature (CINAHL)
 Medical Literature Analysis and Retrieval System Online (MEDLINE)
 PubMed Central (PMC)
The aforementioned electronic databases and search engines were selected due to their
relevance to the bioscience and healthcare domain. Published literature were only cited in
these databases. With the aim of averting publication bias, which in turn would create an
impact on the literature review, grey literature search was also conducted from additional
sources that are given below:
 Google Scholar
Key terms
The major search terms that were used for retrieving relevant literature from the databases
were ‘urinary tract infection’, ‘UTI’, ‘elderly’, ‘old patients’, ‘antibiotics’, ‘therapy’,
‘prophylaxis’, ‘antibacterial’, ‘recurrence’, and ‘relapse’. In order to ensure that all possibly

11INDEPENDENT STUDY
pertinent literature was acknowledged, several search strategy augmenting practices were
used, including:
 searching for a grouping of applicable keywords and their synonyms by ‘medical
subject heading’ (MeSH) and free-text terms, without or with the use of truncation
(‘$’ or ‘*’) for facilitating the addition of stem words
 probing for catchphrases in quotation symbols; and
 usage of Boolean operators (AND, NOT, and OR) for combining keywords
(McGowan et al. 2016).
Inclusion and exclusion criteria
Articles obtained from the databases were considered pertinent only upon meeting a
pre-determined criteria that helped in recognising the scholarly evidences that were
prospective for the research question. Any articles that could not meet the criteria were
excluded from the review (Moule, Aveyard and Goodman 2016). The table provided below
illustrates the inclusion and exclusion criteria for articles that were included in this systematic
review:
Criteria Quantitative research Qualitative research
Inclusion criteria Published in English Published in English
Published between 2010-till
date
Published between 2010-till
date
Any country of publication Any country of publication
Focuses on elderly patients
having UTI
Focuses on elderly patients
having UTI
With full-text availability With full-text availability
Focus on antibiotic therapy Focus on antibiotic therapy

12INDEPENDENT STUDY
Represents effects of
antibiotics in treating UTI in
terms of statistical data
Represents impacts of
antibiotic prophylaxis in
management of UTI in terms
of thematic or narrative
analysis
Exclusion criteria Published in foreign language Published in foreign language
Published prior to 2010 Published prior to 2010
Focusing on UTI among
patient population, other than
elderly
Focusing on UTI among
patient population, other than
elderly
Abstracts, manuscripts Abstracts, manuscripts
Table 2- Inclusion and exclusion criteria for literature review
Literature review results
The table given below summarises the information collected from the selected articles
in a tabular format:
Auth
ors
Aim Setting
and
populatio
n
Outcome
measures
Results Conclusi
on
Implica
tion
Ahm
ed et
al.
(2017
)
To
investiga
te the
clinical
uncertai
nties
Systemati
c review
conducted
by
searching
articles
UTI relapse per
patient-year was
the primary
outcome during
prophylaxis.
Secondary
No trials
focused on
older men. 3
RCTs equated
long-term
antibiotic
Long-
term
antibiotic
administr
ation
decreases
Nurses
should
be
trained
on steps
that

13INDEPENDENT STUDY
associate
d with
safety
and
efficienc
y of
long-
term
antibioti
c
prophyla
xis for
averting
recurring
urinary
tract
infection
s (UTIs)
amid
older
adults
from
CINAHL,
MEDLIN
E, Embase
and
Cochrane
Register
of
Controlled
Trials.
Articles
selected
from
inception
till August
2016. 4
RCTs
were
considered
eligible
for
inclusion
in the
analysis.
outcome focused
on proportion of
patients having
experienced at
least 1 relapse,
following
prophylaxis
period, duration
to first relapse,
and patient
proportion with
antibiotic
resistance
prophylaxis
with oral
lactobacilli
(n=238), D-
mannose
powder (n=94),
and vaginal
oestrogens
(n=150). These
antibiotics
lowered risks
of UTI relapse
by 24% [(RR)
0.76; 95% CI
0.61-0.95]. No
statistically
significant
upsurge in risks
of side effects
due to
antibiotic use. 1
RCT
demonstrated
antibiotic
resistance to
the
danger of
relapse in
postmeno
pausal
females
with
repeated
UTI.
need to
be
adopted
upon
encount
ering
antibioti
c-
resistan
ce in
UTI
affected
older
patients

14INDEPENDENT STUDY
trimethoprim-
sulfamethoxazo
le.
Ahm
ed et
al.
(2018
)
To
determin
e the
prevalen
ce of
antibioti
c
prophyla
xis and
associate
d
clinical
outcome
s amid
older
adults
suffering
from
repeated
UTI
Retrospect
ive cohort
study
conducted
by using
records of
19,696
adults
aged more
than 65
years, and
with
recurring
UTIs.
Prescription
records used for
ascertaining
prophylaxis
greater than 3
months for
cephalexin,
trimethoprim, or
nitrofurantoin.
Cox recurrent
event model used
for hazard ratio
(HR) estimation.
Primary outcome
was clinical
recurrence.
Secondary
outcomes were
hospitalisation
and acute
antibiotic
prescribing
12.6% (508)
men and 14.2%
(2229) women
had been
prescribed
antibiotic
prophylaxis.
This was
related with a
significant
reduction in
risks of clinical
relapse in
males (HR,
0.54; 95% CI,
0.51–0.57), and
UTI-associated
hospitalisation
(HR, 0.78; 95%
CI, 0.64–
0.94). Clinical
recurrence of
Antibioti
c
prophyla
xis was
correlated
with
decreased
rates of
relapse of
UTI and
acute
antibiotic
prescripti
on among
older
adults.
Further
research
must be
conduct
ed for
ascertai
ning
impacts
of
antimicr
obial
resistan
ce on
patients
and
incidenc
e of
antibioti
c-
associat
ed
adversat

15INDEPENDENT STUDY
UTI also
decreased
among females
(HR, 0.57; 95%
CI, 0.55–0.59).
ive
events
Beve
ridge
et al.
(2011
)
To
determin
e the
epidemi
ology,
diagnosi
s and
treatmen
t of UTI
among
the
elderly
Narrative
review
Comprehensive
review conducted
for 43 pieces of
scholarly
evidences.
Antimicrobial
prescribing was a
major outcome
related to the
domain of UTI
management
Owing to the
augmented
difficulties with
health care
associated
infection and
resistance, the
administration
of narrow
spectrum
antimicrobials
is strongly
encouraged.
Trimethoprim
should be
administered as
a first-line
antibiotic
among older
females
Glitches
with
antimicro
bial
resistance
can be
easily
attempted
with
judicious
administr
ation of
antibiotic
s such as,
-
trimoxaz
ole,
trimethop
rim, and
nitrofuran
Nurses
should
gain a
sound
understa
nding of
the
differen
t
antibioti
cs that
they
should
adminis
ter for
lowerin
g the
rates of
recurrin
g UTI

16INDEPENDENT STUDY
suffering from
uncomplicated
symptomatic
UTI. Another
alternative that
has proven
efficacy for
UTI
management is
nitrofurantoin.
However, it
must not be
administered
among older
adults having
renal
impairment.
Trimethoprim-
sulfamethoxazo
le is also
effective for
treating acute
symptomatic
lower UTI
among women
toin among
the
elderly
patient
populati
on

17INDEPENDENT STUDY
for initial three
days. Upon
observing
antibiotic
resistance
among older
patients, a
combination of
nitrofurantoin
and fosfomycin
must be used
Crelli
n et
al.
(2018
)
To
explore
if usage
of trimet
hoprim
ofr UTI
treatmen
t is
associate
d with
augment
ed risks
of
hyperkal
Cohort
study
conducted
based on
primary
care
records of
the UK
that
focused on
adults
aged more
than 65
years and
Death, acute
kidney injury,
and
hyperkalaemia,
within 2 weeks
of treating UTI
with antibiotics
were the primary
outcomes
178238 persons
were
recognised with
at least one
UTI managed
with
antibiotics.
Acute kidney
injury odds
were greater
after
trimethoprim
(OR1.72,
95%CI; 1.31-
For 1000
UTIs
managed
with
antibiotic
s amid
older
adults,
treatment
with
trimethop
rim rather
than
amoxicill
Nurses
should
gain
knowle
dge on
the
effectiv
e
dosage
and
duration
of
adminis
tration

18INDEPENDENT STUDY
aemia,
acute
kidney
injury,
or
sudden
death
with
prescriptio
n for
amoxicilli
n,
ciprofloxa
cin,
cefalexin,
trimethopr
im, or
nitrofurant
oin,
following
UTI
diagnosis
2.24) and
ciprofloxacin
administration
(OR1.48, 1.03-
2.13), in
contrast to
amoxicillin.
Trimethoprim
usage showed
high odds of
hyperkalaemia.
in would
lead to 1-
2 extra
cases of
hyperkala
emia and
2
instances
of acute
kidney
injury,
of these
antibioti
cs to
reduce
the
occurre
nces of
kidney
injury
and
hyperka
laemia
Drek
onja
et al.
(2013
)
To study
UTI
treatmen
t and
clinical
outcome
s among
veteran
males
Cohort
study that
focused on
Veterans
Affairs
administra
tive data
for the
fiscal year
2009
Episodes of UTI
were
characterised as
early recurrence
(<30 days),
index, and/or late
recurrence (≥30
days) instances.
Name of the
antibiotics,
Antimicrobial
agents that
were used
maximum were
ciprofloxacin
(62.7%) and
trimethoprim-
sulfamethoxazo
le (26.8%). Of
the patients
Long-
duration
antibiotic
treatment
(>7 days)
for older
males
affected
with UTI
in
Prior to
adminis
tration
of long-
term
antibioti
cs,
nurses
should
determi

19INDEPENDENT STUDY
duration of
treatment and
outcomes
(Clostridium
difficile infection
during 1 year and
recurrence) were
measured
65% received
long-duration
treatment (>7
days), and 35%
short-duration
treatment (≤7
days). 4.1%
index cases
were associated
with early
relapse and
9.9% with late
relapse of UTI.
Increased late
relapse
observed with
short-duration
treatment
(10.8% vs
8.4%, P < .001)
. No significant
relapse
observed
among patients
who were
outpatient
settings
was
meaningf
ully
associate
d with no
decrease
in late or
early
recurrenc
e
ne the
risks for
CDI
infectio
n

20INDEPENDENT STUDY
subjected to
long-duration
antibiotics.
Nonetheless,
long-duration
treatment was
associated with
risks of
C.difficile infec
tion
Mali
k et
al.
(2018
)
To
explore
the
impacts
of
antibioti
c allergy
amid
older
women
with
recurring
UTI, for
fitting
choice
Prospectiv
e cohort
study
based on a
database
that
contained
informatio
n from
females
aged more
than 65
years,
with
document
Primary outcome
focused on drug
allergies,
antibiotic
susceptibility of
urine culture,
renal function,
resistance to
fluoroquinolones,
nitrofurantoin,
and
trimethoprim-
sulfamethoxazole
(TMP-SMX)
The proportion
of older
females
resistant,
allergic, or both
resistant and
allergic
to fluoroquinol
ones was 34%,
14%, and 8.1%;
to TMP-SMX
was 29%, 34%,
and 15%; and
to
nitrofurantoin
Owing to
the
presence
of
antibiotic
resistance
/allergy
numerous
first-line
antibiotic
s are not
obtainabl
e for
several
older
Nurses
should
gain a
sound
understa
nding
on the
efficacy
of
nitrofur
antoin
for UTI
treatme
nt.

21INDEPENDENT STUDY
of oral
antibioti
c
treatmen
t
ed UTI
and
trigonitis
on cystosc
opy
was 14%, 16%,
and 5%,
respectively.
Sensitivity to
nitrofurantoin
was
demonstrated
by 20%
females who
were resistant
and/or allergic
to both the
drugs.
Increased
proportion of
other antibiotic
resistance was
observed
among those
who were
resistant or
allergic to
TMP-SMX
(4.9 ± 3.6 vs
2.1 ± 2.3; P
females
with
recurrent
UTIs.

22INDEPENDENT STUDY
< .0001).
Mod
y and
Jutha
ni-
Meht
a
(2014
)
To
review
the
treatmen
t of
sympto
matic
UTI and
asympto
matic
bacteriur
ia, and
preventi
on
strategie
s of
relapsing
UTI
among
commun
ity-
dwelling
aged
women
Comprehe
nsive
literature
review
conducted
by
thorough
search of
Ovid
(Medline,
PsycINFO
,
Embase) d
atabases
for pieces
of
scholarly
databases
that were
published
in English,
between
1946-
2013.
Asymptomatic
bacteriuria has
been recognised
transient among
older women,
which most often
resolves without
adequate
treatment.
Effecitve
treatment of
asymptomatic
bacteriuria has
been found
effective in
eradicating
bacteriuria.Nonet
heless, adverse
antimicrobial
drug reaction,
rates of
reinfection (1.67
vs 0.87 per
patient-year of
Antibiotics are
typically
designated by
recognising the
uropathogen,
determining
rates of local
resistance, and
taking into
consideration
adverse impact
profiles.
Chronic
oppressive
antibiotics for
6-12 months
and vaginal
estrogen
therapy
efficiently
decreases
episodes of
symptomatic
UTI and should
Asympto
matic
bacteriuri
a should
not be
treated in
older
women
and
should be
clearly
distinguis
hed from
symptom
atic UTI
Nurses
should
take
into
consider
ation
the
resistan
ce
observe
d
among
older
females
to
differen
t
antibioti
cs

23INDEPENDENT STUDY
follow-up), and
isolation of
progressively
resistant
microorganisms
have been found
to be more
prevalent more
among therapy
groups, in
contrast to non-
therapy groups.
Fluoroquinolone
is one of the
most prescribed
antibiotics to
older adults
suffering from
UTI and its
resistance is
maximum for the
target population.
Furthermore,
incidence of
E.coli isolates
also be
considered for
older patients
with recurring
UTI.

24INDEPENDENT STUDY
that are resistant
to
fluoroquinolones
in combination
with
trimethoprimsulf
amethoxazole
has demonstrated
an upsurge from
274-512/100,000
person-years (P <
.05).
Trimethoprim-
sulfamethoxazole
administration
for 3 days has
been recognised
as the mainstay
for UTI therapy.
In addition,
nitrofurantoinas
also acts as a
first-line agents
for UTI
treatment.

25INDEPENDENT STUDY
Myri
am et
al.
(2019
)
To
explore
the
correlati
on
between
antibioti
c
treatmen
t for UTI
and
adverse
health
outcome
s among
elderly
patients
residing
in
primary
care
Retrospect
ive cohort
study that
was based
on
primary
records
from
Clinical
Practice
Research
Datalink
(2007-
2015) and
comprised
of 157264
older
adults who
had at
least one
record of
confirmed
or
suspected
UTI
Hospital
admission,
bloodstream
infection, and all-
cause mortality
that occurred
within 60 days
following index
UTI diagnosis
were the major
outcome
measures
Of the 312896
episodes of
UTI (157264
unique
patients), an
estimated 7.2%
(n=22 534)
failed to
reproduce any
record of being
prescribed
antibiotics; In
contrast 6.2%
patients
(n=19292)
manifested a
delay in
antibiotic
prescribing. An
estimated 1539
episodes
(0.5%) of
bloodstream
infection were
chronicled
Among
elderly
patients
in
primary
care, who
have been
diagnose
d with
UTI,
deferred
antibiotic
s and no
antibiotic
s were
allied
with a
notewort
hy
upsurge
in all-
cause
mortality
and
bloodstre
Nurses
should
take
precauti
onary
steps
while
adminis
tering
antibioti
cs to
males
aged
more
than 85
years,
as they
have
high
risks for
all-
cause
mortalit
y and
bloodstr

26INDEPENDENT STUDY
within two
months after
initial
UTI. Significan
tly high rates of
bloodstream
infections were
observed
among patients
who were not
given any
antibiotics
(2.9%; n=647).
Following
covariate
adjustment,
patients
manifested an
increased
likelihood of
experiencing
infection in no
antibiotic (OR
8.08, 7.12 to
9.16) and
am
infection,
equated
with
immediat
e
antibiotic
s.
eam
infectio
n

27INDEPENDENT STUDY
deferred
antibiotic group
(OR7.12,6.22
to 8.14). Lack
of antibiotic
administration
also increased
the rate of
admission to
hospitals
(27%), when
compared to
those older
patients who
had been
immediately
prescribed
antimicrobials,
after UTI
detection. Risks
of all-cause
mortality were
also greater
among those
who had not

28INDEPENDENT STUDY
been prescribed
antibiotics.
Rowe
and
Jutha
ni-
Meht
a
(2014
)
To
explore
the
diagnosi
s and
treatmen
t
strategie
s for
UTI
among
older
adults
Comprehe
nsive
review
conducted
Different
diagnostic
techniques and
management
strategies were
the major
outcomes
For older
women who
reported
nonspecific
symptoms of
UTI, hydration
and
interruption in
empiric
antibiotic
administration
must be
encouraged by
physicians,
until a analytic
workup for UTI
is performed.
For the
treatment of
uncomplicated
UTI among
older adults,
100 mg of
Selecting
necessary
antimicro
bial
agents is
essential
for older
adults
Nurses
should
increase
knowle
dge on
the
duration
and
dosage
of
antimicr
obial
adminis
tration
for
minimis
ing
adverse
effects
of the
medicat
ions in
the

29INDEPENDENT STUDY
Nitrofurantoin
monohydrate/m
acrocrystals
must be
administered
twice daily, for
5 days. The
antibiotic
management
should also
encompass
160/800 mg
from
TMP/SMX, for
3 consecutive
days, twice
daily.
Administration
of 3g
fosfomycin in
the form of a
single dose is
also
recommended.
Additionally,
elderly

30INDEPENDENT STUDY
nitrofurantoin
is effective for
management of
UTI amid older
adults having
creatinine
clearance
higher than 40
mL/min
Table 3- Summary of articles included in the review

31INDEPENDENT STUDY
Chapter 3: Methodology
This chapter summaries the methodological strategies and approaches that had been
adopted for this research. The sections presented in this chapter have been briefly explained,
along with definite rationale for conducting them. The methods have also been described
along with the data analysis procedures that have been followed, to obtain the expected
results for the investigation under phenomenon.
Research methodological approaches
Research methodological approaches are rightly described as frameworks that help in
collating broad assumptions related to research, into a detailed and comprehensive plan,
along with data collection process, analysis of the collected data, and interpretation of the
results (Kumar 2019). It has been found that diverse research questions and theories request
the acceptance and implementation of a range of research approaches. The research
procedural approaches can be either qualitative, quantitative, or mixed methods (Creswell
2014). The qualitative research approach is typically useful during the conduction of
systematic reviews, owing to the fact that they encompass a naturalistic enquiry that
facilitates seeking an in-depth awareness and understanding of the phenomenon that is being
investigated. The primary objective of using a qualitative research approach can be accredited
to the fact that it facilitated the assortment of comprehensive data about on the extent of
efficacy of long-term antibiotics that help in preventing the relapse of UTI among the elderly,
which in turn addressed the primary research question. To conduct such a wide ranging
investigative research with the use of quantitative methods would increase the possibility of
glitches, allied with manifold significance testing, counting in analysing several variables that
might produce false positive results (Flick 2015). Another disadvantage of adopting a
quantitative survey approach is that it would require a prior insight for conducting the
examination among UTI affected elderly patients. Another important feature of conducting a

32INDEPENDENT STUDY
review was that it helped in the interpretation and explanation of the phenomena, in relation
to the effect that are brought about in the target population (Bresler and Stake 2017).
Inductive reasoning
Also referred to as inductive approach, this procedure typically begins with
observation, followed by theories being proposed towards the culmination of the research
investigation, collected from observation (McAbee, Landis and Burke 2017). Adoption of an
inductive approach involved conducting a comprehensive search for specific patterns of
information from observing several research studies, and also encompassed developing
explanations for elucidation of the patterns obtained during the research. No hypotheses or
theories were employed at the beginning of the review, which provided the discretion to
divert the direction of the investigation, after commencing the research process.
It should be mentioned that inductive research approach does not merely apply to
disregarding hypotheses and theories during formulation of a research question, aims, and
objectives. In contrast, this approach facilitated the generation of definite meanings from
datasets, which have been collected during the research, with the sole purpose of identifying
relationships and patterns, and building a theory (Jebb, Parrigon and Woo 2017).
Nonetheless, this approach did not prevent usage of already existing theories for development
of the research question, intended to be explored. Hence, while conducting this systematic
review, the first step involved beginning with a research topic, followed by developing
observed generalisations, and identification of preliminary associations, with a progress in the
investigation. The figure provided below demonstrates the bottom-up strategy that was
involved in the research, whereby observations from several scholarly pieces of evidences
were used for building an abstraction and describing a picture of the phenomenon that was
being investigated.

33INDEPENDENT STUDY
Figure 1- Inductive approach
The table provided below elaborates on the concepts that were associated with adoption of an
inductive approach for the purpose of conducting this systematic review:
Characteristics Concepts related to the review
Type of question Open-ended
Type of reasoning Induction
Type of analysis Narrative description
Table 4- Perspective of the inductive research approach
Research paradigm
According to Rose, Spinks and Canhoto (2014) research paradigm encompasses the
manner of describing the world view, which in turn gets informed by holding philosophical
assumptions regarding the type of social reality, different procedures of knowing, and the
value systems associated with research. Particular paradigms have been associated with
different research methodologies. No one theoretical or paradigmatic framework has been
recognised as correct, and determination of paradigmatic view helps in informing the
research design, to best respond the phenomenon under study. The figure given below
highlights the different factors that influence the selection of research paradigm:
Tests/Observations Patterns and Themes Theory

34INDEPENDENT STUDY
Figure 2- Factors that influence research paradigm
An interpretive research paradigm was developed for the purpose of conducting this
systematic review. Interpretive researchers hold the belief that reality comprises of subjective
experiences of people related to the external world. This results in the subsequent adoption of
an inter-subjective ontological and epistemological belief that realism is socially built. In
other words, interpretivists have been recognised as anti-foundationalists, who hold the
assumption that there does not exist any lone method or correct route for knowledge
(Chowdhury 2014). Therefore, an interpretive tradition was adopted for this systematic
review, whereby there was no right or improper theory. Attempts were taken to derive
constructs from the domain, by conducting thorough examination of the research
phenomenon of interest. Therefore, the paradigm involved in this systematic review was
underpinned by interpretation and observation of data from already published scholarly
articles, thereby facilitating drawing inferences by arbitrating the match between the collected
information and their patterns (Potrac, Jones and Nelson 2014). The table provided below
describes the characteristics of the research paradigm adopted for this systematic review:
Character Description
Paradigm
Assumptions on the
nature of knoweldge
and reality
Ethical principles
and value system
Research practice and
theoretical framework

35INDEPENDENT STUDY
Research purpose Interpreting the effects of long-term
antibiotic therapy in reducing relapse of UTI
among elderly patients
Ontology There are several realities that can be
constructed and explored through
meaningful actions
People views, knowledge, experiences and
interpretation lead to variation in social
realities
Epistemology Interaction with different social context
governs several events.
Natural settings are utilised for data
collection
Methodology Systematic review
Table 5- Interpretivism characteristics
Data collection
Extraction of articles involved conducting a comprehensive search of three electronic
databases namely, PMC, CINAHL, and MEDLINE. In addition to the databases, Google
scholar was also used for retrieving scientific literature. The major search terms that were
combined with boleean operators AND and OR were ‘urinary tract infection’, ‘UTI’,
‘elderly’, ‘old patients’, ‘antibiotics’, ‘therapy’, ‘prophylaxis’, ‘antibacterial’, ‘recurrence’,
and ‘relapse’. Use of truncation (‘$’ or ‘*’). The Preferred Reporting Items for Systematic
Reviews and Meta-Analyses, commonly referred to as PRISMA was adopted for reporting
and refining the wide array of scholarly literatures that had been extracted from the databases

36INDEPENDENT STUDY
and search engines. It facilitated complete and transparent reporting of the research (Moher et
al. 2015).
Use of PRISMA flowchart enabled bringing about an improvement in the reporting
quality of systematic review, by providing considerable transparency in the assortment
process of articles in a systematic review. This in turn enhanced reliability of the findings and
value of the collected medical research based literature. At the end of data collection, nine
articles were considered suitable for addressing the research question. The figure provided
below provides a graphical representation of data collection:
Figure 3- PRISMA flow chart

37INDEPENDENT STUDY
Data analysis
The framework of GRADE (Grading of Recommendations, Assessment,
Development and Evaluations) approach was followed for development and presentation of
the summaries of collected evidence. The rationale behind using this approach can be
elucidated by the fact that it has been widely recognised as efficient, for grading the evidence
quality and suggesting recommendations (Morgan et al. 2016). GRADE commonly has four
different levels of evidence namely, very low, low, moderate, and high, and cannot be
implemented mechanically. Therefore, the articles obtained from database search were
evaluated to find presence of risk of bias, indirectness, inconsistency, imprecision, and
publication bias. The table provided below suggests the reasons that rate evidences high or
low:
Rating down Rating up
Imprecision Dose-response gradient
Risk of bias Large magnitude effect
Inconsistency Residual confounding increases effect
magnitude
Publication bias
Indirectness
Table 6- Reasons for rating evidence quality up or down
An analysis of the nine articles selected from the databases suggest that there were
five cohort studies and four reviews. Hence, the articles included were of high and moderate
quality of evidence (Neumann et al. 2015). This was in accordance to the guidelines enforced
in the GRADE approach that is provided below:
Quality Interpretation

38INDEPENDENT STUDY
High The true effect is close to estimate of that
effect
Moderate The true effect shows a likelihood of being
close to the effect estimate, but there lies a
probability that it is considerably different
Low The true effect might be noticeably different
from the effect estimate
Very low The true effect is expected to be noticeably
diverse from the effect estimate
Table 7- GRADE ratings of the quality of evidence and their interpretation
Following determination of the quality of evidences that had been collected for the
research, the process of thematic analysis was used for making a sense of the information
collected from all scholarly evidences. This helped in analysing the information presented in
all articles and facilitated a systematic gain of knowledge about the research question. The
basic objective of conducting a thematic analysis can be accredited to the fact that it generally
assists researchers in moving from a comprehensive interpretation of collected data, towards
noticing patterns and outlining a specific conclusions (Braun et al. 2019). Thematic analysis
encompass examination, identification, and recording different data patterns from the
research results that are considered imperative for describing the phenomenon being
investigated. Thus, identifying themes from the article results helped in drawing definite
meanings about the impacts of long-term antibiotic therapy on relapse of UTI among older
adults.

39INDEPENDENT STUDY
Chapter 4: Results
This chapter presents the findings collected from the nine articles included in the
systematic review, through the identification, analysis and reporting of patterns or themes.
The method of thematic analysis is independent and descriptive in nature, besides contained
detailed information on research results. Thematic analysis has been identified imperative in
conducting systematic reviews that are based on perspectives. The process also took into
consideration the fact that the reality concerning a particular phenomenon (long-term effects
on antibiotic therapy on UTI relapse), has been indexed at a location within the collected
data. The six step approach that resulted in the development of three themes from the
scholarly evidences collected are given below:
Figure 4- Thematic analysis process
Most effective antibiotics
Ahmed et al. 2017 conducted a systematic review to determine the impacts that long-
term antibiotic therapy exerts on averting recurrence of UTI among older adults. Conduction
of a systematic search in several electronic databases made them suggest that nitrofurantoin
and trimethoprim– sulfamethoxazole were the two most prevalent antibiotics that elderly
Famili
arisati
on
Gener
ation
of
initial
codes
Search
ing for
themes
Search
ing for
theme
s
Revie
wing
the
theme
s
Them
e
namin
g

40INDEPENDENT STUDY
patients were generally administered, for lowering their chances of facing a UTI relapse. It
was suggested by the researchers that 50mg and 100mg nitrofurantoin capsules were typically
administered to the patients at night. They also provided evidence for the prescription and
administration of 480mg tablets of trimethoprim– sulfamethoxazole at night to the older
patients, for an estimated period of 12 months, with the aim of lowering UTI relapse rates.
This was in accordance with the findings presented by Ahmed et al. (2018) who
demonstrated the effects of three different antibiotics on the elderly patients. These
researches subjected male and female patients to trimethoprim, nitrofurantoin, and
cephalexin, as per recommended intake doses formulated by the BNF.
While elucidating on the techniques used for management of UTI through the
administration of antimicrobials, it was postulated by Beveridge et al. (2011) that usage of
narrow spectrum antimicrobial agents proves most effective in reducing chances of being
infected with Clostridium difficile. Results from the study highlight the fact that trimethoprim
is the most recommended antibiotics that has been advocated for preventing UTI recurrence.
In addition, they also identified nitrofurantoin as an effective alternative. Furthermore, the
researchers also recommended showing adherence to the European guidelines that highlight
the importance of administering fosfomycin trometamol and nitrofurantoin, in combination
with trimethoprim or cotrimoxazole, under cases that demonstrate >20% resistance rates. Use
of the combination antibiotic co-trimoxazole that comprises of a combination of
sulfamethoxazole and trimethoprim was identified in another cohort study. The researchers
elaborated on the efficacy of five antimicrobials in lowering UTI recurrence rates among the
elderly namely, trimethoprim, ciprofloxacin, cefalexin, amoxicillin, and nitrofurantoin, thus
showing accordance with the aforementioned investigations (Crellin et al. 2018).
Findings from the original investigation conducted by Drekonja et al. (2013)
suggested that some common antibiotics used to treat UTI in the elderly were namely,

41INDEPENDENT STUDY
fluoroquinolone, trimethoprim-sulfamethoxazole, and β-lactam. Although previous studies
had shed light on the use of the first two antibiotics, there was little evidence on the efficacy
of β-lactam in treating UTI. Furthermore, Malik et al. (2016) opined that trimethoprim-
sulfamethoxazole, sulphonamides, nitrofurantoin, and fluoroquinolones like moxifloxacin,
levofloxacin, and ciprofloxacin were effective antibiotics against UTI recurrence. This was
congruent with the findings presented by Mody and Juthani-Mehta (2014) who recommended
the administration of daily 50 mg nitrofurantoin for a year, 100mg trimethoprim, and 40
mg/200 mg trimethoprim-sulfamethoxazole for six months. The same was stated by Rowe
and Juthani-Mehta (2014) who proposed the use of 160/800 mg trimethoprim-
sulfamethoxazole, 3g fosfomycin, and 100 mg nitrofurantoin monohydrate for UTI
management among community dwelling elderly patients. Apart from the ones stated above,
some other antibiotics that were prescribed by Myriam et al. (2019) were pivmecillinam,
macrolides, aminoglycosides, polymyxin, and clindamycin.
Extent of reduction of UTI
According to the findings presented by Myriam et al. (2019) nitrofurantoin was
established as an effective antimicrobial agent for the management and treatment of UTI in
elderly patients, having creatinine clearance larger than 40 mL/min. However, they suggested
that long-term antibiotic therapy among male veterans for a duration greater than seven days,
was not noticeably associated with a lessening in the rates of UTI recurrence, upon
comparing them with short-term therapeutic intervention (less than seven days). According to
Myriam et al. (2019) rates of bloodstream associated infection significantly increased
significantly among the 647 patients who had not been administered any antibiotics (2.2%),
in comparison to those patients who had been prescribed antimicrobials during initial
consultations (0.2%). Additionally, immediate antibiotic administration was also associated
with low rates of hospital readmissions (14.8%) and all-cause mortality, thereby determining

42INDEPENDENT STUDY
their long-term effects. Findings presented by Mody and Juthani-Mehta (2014) highlighted
the fact that there exists lack of difference in clinical failure rates between long-course (7–14
days) and short course (3–6 days) antibiotic therapy for managing UTI among older women.
Although the researchers highlighted the fact that single-dose antimicrobial therapy was
usually preferred by most elderly patients, persistent UTI rates was suggestively greater with
single-dose therapy, in comparison to short-course therapy (RR, 2.01; 95% CI, 1.05–3.84).
Drekonja et al. (2013) suggested that of the 35.0% of patients who had been administered
short duration antibiotic treatment (>7 days), and 65.0% patients receiving long duration
treatment (<7 days), 4.1% instances were followed by early UTI recurrence and 9.9% by late
UTI recurrence. In addition, long duration antibiotic failed to bring about a reduction in late
or early recurrence of UTI, in comparison to short-term therapy (10.8% vs 8.4%, P.001).
Crellin et al. (2018) also highlighted that following antibiotic initiation among elderly
patients suffering from UTI, increased likelihood of renal impairment were observed among
those who were subjected to ciprofloxacin (OR: 1.48, 95% CI: 1.03-2.13) and trimethoprim
(OR:1.72, 95% CI: 1.31-2.24) a drug, when compared to amoxicillin antibiotic. Therefore,
besides determining the fact that trimethoprim is effective in treating UTI among older
people, the findings also suggested that there was 1.12 odds of death, within two weeks of
antibiotic administration. Findings published by Ahmed et al. (2018) also suggested that
antibiotic prophylaxis was related with a decreased risk of clinical UTI recurrence among
older males (HR, 0.49; 95% CI, 0.45–0.54), less chances of UTI-related hospitalisation (HR,
0.78; 95% CI, 0.64–0.94), and acute antibiotic prescribing (HR, 0.54; 95% CI, 0.51–0.57). In
contrast, although similar results were observed among females, in relation to antibiotic
prescribing and UTI relapse, there was inconsistency related to UTI-related hospitalisation
(HR, 1.16; 95% CI, 1.05–1.28). These results established that long-term antibiotic therapy
were more effective among older men. However, no significant effects of antibiotic

43INDEPENDENT STUDY
administration on older or frail care service residents could be demonstrated by Ahmed et al.
(2017). Although antibiotic prophylaxis proved effective in lowering risks of UTI recurrence
among postmenopausal women, recurrence rates in older patients could not be ascertained.
Antimicrobial resistance
In the study conducted by Ahmed et al. (2017) upon comparing with lactobacilli,
older women who had received a year of trimethoprim–sulfamethoxazole prophylaxis
demonstrated drastic upsurge in the proportion of bacteria, isolated from faeces and urine that
were antibiotic resistant. An estimated 20%–40% of faecal and urinary E coli isolates
demonstrated resistance to trimethoprim, amoxicillin, and trimethoprim–sulfamethoxazole at
baseline, which elevated to 80%–95%, after a month. Cessation of prophylaxis reduced the
resistance levels near baseline. Beveridge et al. (2011) also suggested that fluoroquinolones
must not be recommended to older patients diagnosed with UTI, as first line agents, unless
the patients demonstrated amplified levels of resistance to trimethoprim and/or trimethoprim-
sulfamethoxazole (>10%–20%). It was also proposed that 20% local resistance to
trimethoprim-sulfamethoxazole occurred under circumstances when the older patients had
not been administered any antibiotics, during the previous three months. Drekonja et al.
(2013) did not determine the occurrence of antimicrobial resistance with usage of long-term
antibiotics in UTI affected older patients. Findings from another study also suggested that
there was no noteworthy correlation with the occurrence of antibiotic resistance, antibiotic
allergy, and/or sensitivity, in relation to the ethnicity, age, duration of UTI, and diabetes
among the patients. Older women who demonstrated resistance or hypersensitivity to
trimethoprim-sulfamethoxazole, manifested a significantly increased number of resistance to
other antibiotics as well, in contrast to older women who were found sensitive to
trimethoprim-sulfamethoxazole (4.9 resistances ±3.6 versus 2.1±2.3; p < 0.0001).
Significantly higher rates of antibiotic resistance were also found among women with

44INDEPENDENT STUDY
fluoroquinolone resistance or allergy, when compared to their fluoroquinolone sensitive
counterparts (5.8 resistances ±3.5 versus 2.3±2.5; p < 0.0001). Nonetheless, the researchers
failed to demonstrate any major variations in antibiotic resistance among those who had
nitrofurantoin allergy or resistance, compared to nitrofurantoin sensitive older women
(4.5±3.0 versus 4.2±3.8; p = 0.70) (Malik et al. 2018).
Mody and Juthani-Mehta (2014) elaborated on the fact that nitrofurantoin attains low
plasma concentrations, and effectively maintains low resistance levels, following 60 years of
its administration. Fosfomycin was also recommended for resistant bacterial isolates amid
older adults. This drug was postulated to work against methicillin-resistant S aureus (MRSA),
vancomycin-resistant enterococci (VRE), and extended-spectrum β-lactamase (ESBL)–
generating gram-negative rod bacteria. Myriam et al. (2019) also reported a small but
important elevation in 60-days survival among elderly patients treated with nitrofurantoin,
when compared to trimethoprim, which in turn was accredited to greater resistance to the
latter. Rowe and Juthani-Mehta (2014) also established the presence of lower resistance rates
of nitrofurantoin, in contrast to fluoroquinolones and trimethoprim-sulfamethoxazole, thus
emphasising on its effectiveness as a long-term antibiotic. In addition, Proteus mirabilis were
found to display resistance to nitrofurantoin, thereby making the researchers recommend the
administration of trimethoprim-sulfamethoxazole among patients having a history of gram-
negative infections.

45INDEPENDENT STUDY
Chapter 5: Discussion
In this chapter an overall discussion of the findings and thematic analysis reported
above will be presented, followed by determining whether the results obtained in the previous
sections are in accordance to other research articles. The chapter will therefore determine
reliability of the information gathered from the thematic analysis.
Overall discussion
Before commencing this systematic review, several gaps were identified in relation to
the lack of evidence on the long-term effects that antibiotic prophylaxis exerts on prevention
and management of UTI recurrence among older adults. The aims and research questions put
forth in the initial chapter have been addressed by adopting a qualitative interpretive research
design. The research was based on conducting an exhaustive search for scholarly evidences in
order to determine whether recurrence rates of UTI reduced considerably, upon the
application of antibiotics for a long duration. There were variations in the perceptions of
researchers on the effectiveness of long-term antibiotic therapy in preventing UTI. While
results of some articles included in the thematic analysis suggested that subjecting elderly
patients to antibiotic for a long duration reduced their chances of suffering from blood stream
infections and also enhanced their health by lowering rates of hospitalisations, other research
articles presented results that did not show any significant variation with short-term antibiotic
therapy. The lack of efficacy of long-term antibiotic administration in preventing UTI
recurrence was in accordance with the findings presented by ter Riet et al. (2012) who
compared the effects of antibiotics and lactobacilli and suggested that trimethoprim-
sulfamethoxazole prophylaxis for one months was effective in reducing the rates of UTI, with
1 symptomatic UTI instance occurring during 69.3% of the antibiotic administration. In
contrast, the researchers stated that 79.1% lactobacilli administration was related with one

46INDEPENDENT STUDY
instance of symptomatic UTI recurrence, thereby proving better effectiveness of the latter
treatment regimen, over antimicrobial prophylaxis.
On the other hand, Beerepoot et al. (2013) stressed on the need of long-term non-
antibiotic prophylaxis for preventing recurrence of UTI in hospital settings. The researchers
confirmed the findings of the thematic analysis that antimicrobial resistance was a major
problem encountered during the administration of antibiotics to UTI diagnosed patients. This
called for the need of assessing the effectiveness, safety, and acceptability of non-antibiotic
prophylaxis among UTI adult patients, thereby suggesting that there are promising evidences
for the usage of oral immunostimulant OM-89 in lowering rates of UTI relapse and
eliminating chances of resistance. The thematic analysis findings that focused on the
commonly used antibiotic for UTI management were in congruence to results presented in an
earlier research conducted by Shepherd and Pottinger (2013), who emphasised on the usage
of fosfomycin, trimethoprim-sulfamethoxazole, and nitrofurantoin. Nonetheless, the
researchers also stated that fluoroquinolones should not be administered for UTI management
as first-line antibiotics. This was not in accordance with the results of the thematic analysis
since several articles had emphasised on the efficacy of fluoroquinolones such as,
moxifloxacin and levofloxacin.
Findings from another study suggested that recurrence of UTI could be effectively
prevented by administering regular low dosage antibiotics. It was further stated that the
selection and dosage of antibiotic administration should be decided, based on history of
previous infections, and under the supervision of a local microbiological guidance. The
thematic analysis findings were further confirmed by the fact that most of the instances of
UTI recurrences are generally considered reinfections, in place of failure or relapse of the
initial antibiotic therapy (Gupta and Trautner 2013). Geerlings, Beerepoot and Prins (2014)
also aimed to investigate the different prevention strategies of UTI amid women and

47INDEPENDENT STUDY
highlighted the fact that regular or post-coital administration of low-dosage antibiotics are
effective for lowering the rates of recurrent UTIs among post-menopausal women. Therefore,
this statement was in accordance to the findings that had been presented in the thematic
analysis, in relation to impacts of long duration antimicrobial prophylaxis. The fact that the
thematic analysis also identified the widespread prevalence of antimicrobial resistance among
the patients were also affirmed by the researchers who stated that with an increase in the rates
of resistance of Escherichia coli against several antimicrobial agents, researchers have gained
interest in identifying novel non-antibiotic strategies for preventing UTIs.
Eells et al. (2013) developed a Markov chain Monte Carlo model, with the aim of
determining the effectiveness of five different strategies for recurrent UTI and suggested that
daily administration of the antibiotic nitrofurantoin was most operative in treating patients.
This can be established by the fact that regular nitrofurantoin administration was responsible
for lowering UTI rates to 0.4 UTIs/year, when assessed in 3 UTIs/year model. This was in
contrast to the fact that regular administration of estrogen, cranberry, acupuncture, and
symptomatic self-treatment were not able to show any significant differences in UTI
recurrence rates among the patients. However, the researchers stated that long-term
nitrofurantoin prophylaxis was found to be expensive to the patients, with an estimated cost
of $821/year.
In contrast, Matulay, Mlynarczyk and Cooper (2016) illustrated the fact that
uncomplicated cases of UTIs can be effectively managed by administering a short course of
antibiotic therapy. They suggested that some of the most critical aspects to be taken into
consideration during short-term antibiotic prophylaxis treatment are (i) efficacious agents, (ii)
regional variability in patterns of resistance, and (iii) the possibility of creating “collateral
damage” to the biome of the host microbiome. The researchers also presented findings that
were consistent with those of the thematic analysis, whereby they stated that there are four

48INDEPENDENT STUDY
potential empirical first line antimicrobial agents that need to be administered for lowering
UTI recurrence rates namely, (1) 100 mg nitrofurantoin monohydrate/ macrocrystals twice
daily, for consequtive 5 days, (2) 160/800 mg trimethoprim-sulfamethoxazole, twice daily for
succeeding 3 days, (3) single dosage of 3 g fosfomycin trometamol, and (4) 400 mg
pivmecillinam, twice daily for uninterrupted 5 days.
The findings by den Heijer et al. (2012) were also in accordance with the results
present in thematic analysis sections, in relation to resistance to antibiotics. The researchers
provided evidence for the fact that trimethoprim-sulfamethoxazole administration, three
months before inclusion of female patients with recurring UTI, was significantly correlated
with urine E. coli resistance against trimethoprim (OR 3.9, 1.4–10.5), amoxicillin-clavulanic
acid (OR 4.4, 1.5–13.3), amoxicillin (OR 3.6, 95% confidence interval: 1.3–9.9), and
trimethoprim-sulfamethoxazole (OR 3.2, 1.2–8.5). The researchers also highlighted the
presence of faecal E. coli resistance against trimethoprim (OR 2.0, 1.0–3.7), thus indicating
the fact that previous usage of antimicrobials results in resistance against the pathogens, and
subsequently decreases their efficacy in managing UTI. Saha et al. (2014) also opined that E.
coli was the most prevalent uropathogen (67.1%), succeeded by Klebsiella spp. and
Pseudomonas spp., with 22% and 6% prevalence, respectively. The researchers further
highlighted the ineffectiveness of penicillin against E. coli that caused UTI. Evidences were
also provided for maximal resistance of Klebsiella spp against broad-spectrum penicillin,
followed by third generation cephalosporin and aminoglycosides. These findings were also
congruent with the data on antibiotic resistance discussed in the thematic analysis, and called
for the need of implementing novel non-pharmaceutical approaches for preventing UTI
relapse.
It was further emphasised by Singh et al. (2016) that amid a group of patients who
received trimethoprim-sulfamethoxazole prophylaxis, there was an increase in resistance to

49INDEPENDENT STUDY
trimethoprim-sulfamethoxazole (89%) and amoxicillin (86%), within the initial month of
exposure to the former drug. Results from another research that aimed to investigate UTI
causative pathogens and their susceptibility to antimicrobials also highlighted that gram-
negative and gram-positive bacteria were prevalent among 52.48% and 47.51% UTI patients,
respectively. Evidences on resistance against antibiotics as analysed from the thematic
analysis were in congruent with the fact that highest infection rates were observed in E. coli
(74.32%), Staphylococcus haemolyticus (23.88%), and Enterococcus faecalis (23.38%). In
addition, the researchers also established validity of the results discussed in the previous
sections by postulating that while gram-negative bacterial isolates demonstrated increased
antimicrobial resistance against cefuroxime, gram-positive bacteria were resistant to
linezolid, tigecycline, vancomycin, and nitrofurans (Assafi et al. 2015). Stalenhoef et al.
(2018) also demonstrated the efficacy of long-term administration of intravesical gentamicin
prophylactic treatment mong patients having recurring UTI. Their findings illustrated a
noteworthy reduction in the mean proportion of UTIs from 4.8-1.0, at the time of intravesical
treatment, in addition to a decrease in uropathogen resistance rate from 78%-23%. Therefore,
the fact that upon subjecting patients to antimicrobial prophylaxis for a longer duration helps
in lowering their likelihood of again being affected by UTI was adequately established.
Use of antibiotic suppression for lowering rates of UTI were also confirmed by
Dueñas-Garcia et al. (2016) in a systematic search. An analysis of the articles included in this
systematic search indicated that administration of 100 mg nitrofurantoin was more effective,
in comparison to 50 μg vaginal estrogen pessaries, during the entire course of UTI treatment.
Nonetheless, the researchers did not find any significant difference between the effects of
daily administration of 400/80 mg trimethoprim-sulfamethoxazole, when compared with
twice daily administration of lactobacilli oral capsules, containing 109 cfu Lactobacillus
reuteri RC-14 and Lactobacillus rhamnosus GR-1. According to Foon, Toozs‐Hobson and

50INDEPENDENT STUDY
Latthe (2012) when compared to placebo treatment, prophylactic administration of
antibiotics demonstrated efficacy in lowering the chances of significant bacteriuria (12%
without antibiotics versus 4% with antibiotics, RR 0.35, 95% CI 0.22 to 0.56). However, the
researchers failed to demonstrate any noteworthy changes brought about by antimicrobial
prophylaxis in reducing susceptibility to UTI, thus failing to provide adequate evidence for
the efficacy of long-term antibiotic therapy. Therefore, it can be stated that further research
needs to be conducted to determine the extent to which long-term antibiotic therapy decreases
UTI recurrence among older adults.

51INDEPENDENT STUDY
Chapter 6: Conclusion
As there is adequate evidence on the exact extent by which long-term antibiotic therapy
lowers risks of UTI recurrence among older adults, it can be stated that the findings were not
completely successful in explaining the difference between short-term and long-term
antibiotic prophylaxis. Owing to the nature of the lack of information on the research topic,
as identified in the literature review that included common antibiotics used among older
patients, effects of long term administration of antibiotics, and resistance to antibiotics by
uropathogens, the research employed a systematic investigation approach. This research was
one of the first type that had employed an interpretive approach while searching already
published articles, in order to determine the effects of long-term antibiotic prophylaxis. The
use of systematic review method seemed well suitable to the research aim and objectives. It
facilitated formulation of a research question that had a broad scope and also assisted
synthesis of investigations that were directly associated with the question of interest. In other
words, owing to the fact that systematic reviews are considered one of the strongest types of
scientific evidence, the method was well suited and pertinent to this research question. This
research was quite unique in its intensity and approach and provided the opportunity to
conduct comprehensive search of electronic databases for drawing definite conclusions to the
postulated aims and objectives.
Use of an interpretive approach can be considered as one of the major strengths of this
investigation, whereby the evidences were collected based on experience-near perspectives
where the researchers did not being with concepts that had been determined a priori. In
contrast, the research steps involved exploring new data patterns, concepts and themes that
would emerge from the encounters in the domain (as collected from the research studies that
had been extracted from the electronic databases). In other words, adoption of this
investigation strategy facilitated the analytic disclosure of the effects that are exerted by

52INDEPENDENT STUDY
administration of antibiotics for a long duration, while demonstrating how these effects
configured to the generation of observable and measurable outcomes in the target population
(older patients having UTI). The use of database search as the strategy of data collection
facilitated extraction of hundreds of scholarly evidences on UTI and their management with
antibiotic administration, each having different standpoints of the researchers. The research
was valid, in relation to the quality of evidences that had been collection, by adoption of the
GRADE systematic framework that helped in grading the articles as very low, low, moderate,
and high. Trustworthiness of the systematic review was also ensured by the application of a
rigorous criteria for inclusion of articles that were considered prospective for the
investigation.
Proposing a specific and concise research question was the first step towards ensuring
quality and reliability of the systematic review. With the aim of averting bias in the extraction
of articles from the electronic databases, the search strategy was adequately specified in the
review and included as much facts as possible. Providing necessary details on the use of
keywords and their combination strategy allowed establishment of the fact that similar results
would be obtained when alike research will be conducted in future. Reliability of the
conclusions was determined by the fact that studies that were either of high or moderate
quality evidences. In addition, reviewing the results of numerous articles helped in the
generation of subsequent themes that are given below:
 The research highlighted that UTI is common among older adults who face high risks
of relapse
 Thematic analysis revealed that some of the most effective antibiotics that lowered
recurrence rates of UTI amid older adults were trimethoprim-sulfamethoxazole,
nitrofurantoin, cephalexin, fosfomycin, and fluoroquinolones.

53INDEPENDENT STUDY
 It was also concluded from the thematic analysis that long-term administration of
nitrofurantoin and trimethoprim-sulfamethoxazole brings about a significant reduction
in the rates of UTI recurrence, concomitant with a lessening in the prevalence of
blood stream associated infections and other health complications. Single-dose
antimicrobial prophylaxis was identified as the most preferred treatment regimen by
the older adults.
 The findings from thematic analysis also provided evidences for the widespread
prevalence of antimicrobial resistance in UTI patients. It was found that most E coli
demonstrated resistance to the commonly administered antibiotics such as,
trimethoprim-sulfamethoxazole, amoxicillin, and fluoroquinolones.
However, there were certain inherent limitations related with this research that require to
be addressed. The systematic review was based on a comparatively limited number of
electronic databases for extracting studies that were considered potentially eligible. Hence, it
might happen that several prospective pieces of scholarly evidences were eliminated from the
databases that were not searched. Another potential limitation of this systematic review can
be allied with the fact that there was time and resource constraints that resulted in relaying on
the self-proclaimed investigation approach and results by the authors, thereby introducing
bias. It is typically suggested that correspondence with the authors is imperative while
conducting a systematic review, in order to determine the authenticity of the results that will
be reproduced. Nonetheless, constraint in time prevented any such correspondence. In
addition, there was a need to conduct a meta-analysis where data from all the studies that
were used for thematic analysis would be combined by a statistical procedure. Using this
approach would have facilitated identification of a common impact of long-term antibiotics
on UTI recurrence management.

54INDEPENDENT STUDY
Recommendations
Future research should focus on conducting a meta-analysis for combining the results
related to extent of the degree by which long-term administration of antibiotics prevent the
recurrence of UTI among older adults. Conducting a meta-analysis will largely contribute to
the body of evidence about antibiotic prescribing and their effects. There is a need to conduct
multi-centred randomised controlled trials as well, for analysing the effects that
administration of antibiotics for a long duration will create on the target population, in
comparison to placebo or control treatment. In addition, owing to the fact that several
uropathogens demonstrate increasing resistance towards antimicrobials that subsequently
reduces the efficacy of the antibiotics, future research should also focus on examining the
effects of non-pharmacological interventions in lowering rates of UTI recurrence. Hence,
investigation should be conducted on different alternative medicine strategies that have
infection-fighting properties.

55INDEPENDENT STUDY
References
Ahmed, H., Davies, F., Francis, N., Farewell, D., Butler, C. and Paranjothy, S., 2017. Long-
term antibiotics for prevention of recurrent urinary tract infection in older adults: systematic
review and meta-analysis of randomised trials. BMJ open, 7(5), p.e015233.
Ahmed, H., Farewell, D., Jones, H.M., Francis, N.A., Paranjothy, S. and Butler, C.C., 2018.
Antibiotic prophylaxis and clinical outcomes among older adults with recurrent urinary tract
infection: cohort study. Age and ageing.
Assafi, M.S., Ibrahim, N.M., Hussein, N.R., Taha, A.A. and Balatay, A.A., 2015. Urinary
bacterial profile and antibiotic susceptibility pattern among patients with urinary tract
infection in duhok city, kurdistan region, Iraq. International Journal of Pure and Applied
Sciences and Technology, 30(2), p.54.
Aveyard, H., 2014. Doing a literature review in health and social care: A practical guide.
McGraw-Hill Education (UK).
Beerepoot, M.A.J., Geerlings, S.V., Van Haarst, E.P., Van Charante, N.M. and Ter Riet, G.,
2013. Nonantibiotic prophylaxis for recurrent urinary tract infections: a systematic review
and meta-analysis of randomized controlled trials. The Journal of urology, 190(6), pp.1981-
1989.
Beveridge, L.A., Davey, P.G., Phillips, G. and McMurdo, M.E., 2011. Optimal management
of urinary tract infections in older people. Clinical interventions in aging, 6, p.173.
Braga, L.H., Mijovic, H., Farrokhyar, F., Pemberton, J., DeMaria, J. and Lorenzo, A.J., 2013.
Antibiotic prophylaxis for urinary tract infections in antenatal
hydronephrosis. Pediatrics, 131(1), pp.e251-e261.

56INDEPENDENT STUDY
Braun, V., Clarke, V., Hayfield, N. and Terry, G., 2019. Thematic analysis. Handbook of
Research Methods in Health Social Sciences, pp.843-860.
Bresler, L. and Stake, R.E., 2017. Qualitative research methodology in music education.
In Critical Essays in Music Education (pp. 113-128). Routledge.
Chowdhury, M.F., 2014. Interpretivism in aiding our understanding of the contemporary
social world. Open Journal of Philosophy, 4(03), p.432.
Compton, R.D., 2013. Polypharmacy concerns in the geriatric population. Osteopathic
Family Physician, 5(4), pp.147-152.
Cotter, P.D., Ross, R.P. and Hill, C., 2013. Bacteriocins—a viable alternative to
antibiotics?. Nature Reviews Microbiology, 11(2), p.95.
Crellin, E., Mansfield, K.E., Leyrat, C., Nitsch, D., Douglas, I.J., Root, A., Williamson, E.,
Smeeth, L. and Tomlinson, L.A., 2018. Trimethoprim use for urinary tract infection and risk
of adverse outcomes in older patients: cohort study. bmj, 360, p.k341.
Creswell, J.W., 2014. A concise introduction to mixed methods research. Sage Publications.
den Heijer, C.D., Beerepoot, M.A., Prins, J.M., Geerlings, S.E. and Stobberingh, E.E., 2012.
Determinants of antimicrobial resistance in Escherichia coli strains isolated from faeces and
urine of women with recurrent urinary tract infections. PLoS One, 7(11), p.e49909.
Detweiler, K., Mayers, D. and Fletcher, S.G., 2015. Bacteruria and urinary tract infections in
the elderly. Urologic Clinics, 42(4), pp.561-568.
Drekonja, D.M., Rector, T.S., Cutting, A. and Johnson, J.R., 2013. Urinary tract infection in
male veterans: treatment patterns and outcomes. JAMA internal medicine, 173(1), pp.62-68.

57INDEPENDENT STUDY
Dueñas-Garcia, O.F., Sullivan, G., Hall, C.D., Flynn, M.K. and O'dell, K., 2016.
Pharmacological agents to decrease new episodes of recurrent lower urinary tract infections
in postmenopausal women. A systematic review. Female pelvic medicine & reconstructive
surgery, 22(2), pp.63-69.
Eells, S.J., Bharadwa, K., McKinnell, J.A. and Miller, L.G., 2013. Recurrent urinary tract
infections among women: comparative effectiveness of 5 prevention and management
strategies using a Markov chain Monte Carlo model. Clinical Infectious Diseases, 58(2),
pp.147-160.
Flick, U., 2015. Introducing research methodology: A beginner's guide to doing a research
project. Sage.
Flores-Mireles, A.L., Walker, J.N., Caparon, M. and Hultgren, S.J., 2015. Urinary tract
infections: epidemiology, mechanisms of infection and treatment options. Nature reviews
microbiology, 13(5), p.269.
Foon, R., Toozs‐Hobson, P. and Latthe, P., 2012. Prophylactic antibiotics to reduce the risk
of urinary tract infections after urodynamic studies. Cochrane Database of Systematic
Reviews, (10).
Geerlings, S.E., Beerepoot, M.A. and Prins, J.M., 2014. Prevention of recurrent urinary tract
infections in women: antimicrobial and nonantimicrobial strategies. Infectious Disease
Clinics, 28(1), pp.135-147.
Genao, L. and Buhr, G.T., 2012. Urinary tract infections in older adults residing in long-term
care facilities. The annals of long-term care: the official journal of the American Medical
Directors Association, 20(4), p.33.

58INDEPENDENT STUDY
Gordon, L.B., Waxman, M.J., Ragsdale, L. and Mermel, L.A., 2013. Overtreatment of
presumed urinary tract infection in older women presenting to the emergency
department. Journal of the American Geriatrics Society, 61(5), pp.788-792.
Gupta, K. and Trautner, B.W., 2013. Diagnosis and management of recurrent urinary tract
infections in non-pregnant women. Bmj, 346, p.f3140.
Herr, M., Robine, J.M., Pinot, J., Arvieu, J.J. and Ankri, J., 2015. Polypharmacy and frailty:
prevalence, relationship, and impact on mortality in a French sample of 2350 old
people. Pharmacoepidemiology and drug safety, 24(6), pp.637-646.
Hooton, T.M., 2012. Uncomplicated urinary tract infection. New England Journal of
Medicine, 366(11), pp.1028-1037.
Jebb, A.T., Parrigon, S. and Woo, S.E., 2017. Exploratory data analysis as a foundation of
inductive research. Human Resource Management Review, 27(2), pp.265-276.
Kumar, R., 2019. Research methodology: A step-by-step guide for beginners. Sage
Publications Limited.
Machi, L.A. and McEvoy, B.T., 2016. The literature review: Six steps to success. Corwin
Press.
Malik, R.D., Wu, Y.R., Christie, A.L., Alhalabi, F. and Zimmern, P.E., 2018. Impact of
allergy and resistance on antibiotic selection for recurrent urinary tract infections in older
women. Urology, 113, pp.26-33.
Marques, L.P.J., Flores, J.T., Junior, O.D.O.B., Rodrigues, G.B., de Medeiros Mourão, C.
and Moreira, R.M.P., 2012. Epidemiological and clinical aspects of urinary tract infection in
community-dwelling elderly women. The Brazilian Journal of infectious diseases, 16(5),
pp.436-441.

59INDEPENDENT STUDY
Marschall, J., Carpenter, C.R., Fowler, S. and Trautner, B.W., 2013. Antibiotic prophylaxis
for urinary tract infections after removal of urinary catheter: meta-analysis. Bmj, 346,
p.f3147.
Matulay, J.T., Mlynarczyk, C.M. and Cooper, K.L., 2016. Urinary tract infections in women:
pathogenesis, diagnosis, and management. Current Bladder Dysfunction Reports, 11(1),
pp.53-60.
McAbee, S.T., Landis, R.S. and Burke, M.I., 2017. Inductive reasoning: The promise of big
data. Human Resource Management Review, 27(2), pp.277-290.
McGowan, J., Sampson, M., Salzwedel, D.M., Cogo, E., Foerster, V. and Lefebvre, C., 2016.
PRESS peer review of electronic search strategies: 2015 guideline statement. Journal of
clinical epidemiology, 75, pp.40-46.
Mirsaidov, N. and Wagenlehner, F.M., 2016. Urinary tract infections in the elderly. Der
Urologe. Ausg. A, 55(4), pp.494-498.
Mody, L. and Juthani-Mehta, M., 2014. Urinary tract infections in older women: a clinical
review. Jama, 311(8), pp.844-854.
Moher, D., Shamseer, L., Clarke, M., Ghersi, D., Liberati, A., Petticrew, M., Shekelle, P. and
Stewart, L.A., 2015. Preferred reporting items for systematic review and meta-analysis
protocols (PRISMA-P) 2015 statement. Systematic reviews, 4(1), p.1.
Morgan, R.L., Thayer, K.A., Bero, L., Bruce, N., Falck-Ytter, Y., Ghersi, D., Guyatt, G.,
Hooijmans, C., Langendam, M., Mandrioli, D. and Mustafa, R.A., 2016. GRADE: Assessing
the quality of evidence in environmental and occupational health. Environment
international, 92, pp.611-616.
Moule, P., Aveyard, H. and Goodman, M., 2016. Nursing research: An introduction. Sage.

60INDEPENDENT STUDY
Myriam G., Joseph H.D., Hannah L., Rosalind G., Mariam M., Alan P.J., Alison H.H., Paul
A., 2019. Antibiotic management of urinary tract infection in elderly patients in primary care
and its association with bloodstream infections and all cause mortality: population based
cohort study. BMJ, 364(l525), pp.1-12
Neumann, I., Brignardello-Petersen, R., Wiercioch, W., Carrasco-Labra, A., Cuello, C., Akl,
E., Mustafa, R.A., Al-Hazzani, W., Etxeandia-Ikobaltzeta, I., Rojas, M.X. and Falavigna, M.,
2015. The GRADE evidence-to-decision framework: a report of its testing and application in
15 international guideline panels. Implementation Science, 11(1), p.93.
Potrac, P., Jones, R. and Nelson, L., 2014. Interpretivism. Research methods in sports
coaching, pp.31-41.
Rose, S., Spinks, N. and Canhoto, A.I., 2014. Management research: Applying the principles.
Routledge.
Rowe, T.A. and Juthani-Mehta, M., 2014. Diagnosis and management of urinary tract
infection in older adults. Infectious disease clinics of North America, 28(1), p.75.
Saha, S., Nayak, S., Bhattacharyya, I., Saha, S., Mandal, A., Chakraborty, S., Bhattacharyya,
R., Chakraborty, R., Franco, O.L., Mandal, S.M. and Basak, A., 2014. Understanding the
patterns of antibiotic susceptibility of bacteria causing urinary tract infection in West Bengal,
India. Frontiers in microbiology, 5, p.463.
Shepherd, A.K. and Pottinger, P.S., 2013. Management of urinary tract infections in the era
of increasing antimicrobial resistance. Medical Clinics, 97(4), pp.737-757.
Singh, R., Bemelman, F.J., Hodiamont, C.J., Idu, M.M., ten Berge, I.J. and Geerlings, S.E.,
2016. The impact of trimethoprim-sulfamethoxazole as Pneumocystis jiroveci pneumonia
prophylaxis on the occurrence of asymptomatic bacteriuria and urinary tract infections among

61INDEPENDENT STUDY
renal allograft recipients: a retrospective before-after study. BMC infectious diseases, 16(1),
p.90.
Spellberg, B., Bartlett, J.G. and Gilbert, D.N., 2013. The future of antibiotics and
resistance. New England Journal of Medicine, 368(4), pp.299-302.
Stalenhoef, J.E., van Nieuwkoop, C., Menken, P.H., Bernards, S.T., Elzevier, H.W. and van
Dissel, J.T., 2018. Intravesical gentamicin treatment for recurrent urinary tract infections
caused by multidrug-resistant bacteria. The Journal of urology. Retrieved from
https://www.sciencedirect.com/science/article/pii/S002253471843981X
ter Riet, G., Nys, S., van der Wal, W.M., de Borgie, C.A., de Reijke, T.M., Prins, J.M.,
Koeijers, J., Verbon, A., Stobberingh, E. and Geerlings, S.E., 2012. Lactobacilli vs antibiotics
to prevent urinary tract infections: a randomized, double-blind, noninferiority trial in
postmenopausal women. Archives of internal medicine, 172(9), pp.704-712.
Williams, G. and Craig, J.C., 2011. Long‐term antibiotics for preventing recurrent urinary
tract infection in children. Cochrane Database of Systematic Reviews, (3).