Effectiveness Of Adolescent Specific Community Health Services And Long-term Antibiotic Therapy For Urinary Tract Infections

Adolescent Specific Community Health Services

Urinary tract infections occur due to the action of microbes, specifically bacteria and few fungi and are one of the most common infections that affects humans. This infection primarily affects the lower portions of the urinary tract and is also referred to as bladder infection or cystitis (Foxman 2013). The most common cause for UTI is Escherichia coli, and certain risk factors such as, obesity, diabetes, female anatomy, family history, and sexual intercourse. According to Foxman (2014) some of the common symptoms of UTI include burning sensation with urination, bloody urine, cloudy urine, pelvic pain, increased urgency, and rectal pain. Most uncomplicated cases of UTIs are provided treatment with short course of antibiotics namely, trimethoprim/sulfamethoxazole or nitrofurantoin (Flores-Mireles et al. 2015). Resistance to the antibiotics that are commonly administered for treating this condition is increasing at an alarming rate.

Under circumstances when the patient suffers from complicated UTI incidence, intravenous or longer course of antibiotic administration is often required. Administration of phenazopyridine often helps with the management of symptoms (Rowe and Juthani-Mehta 2014). Older women and men are commonly prescribed antibiotics for preventing recurrent urinary tract infections. Use of antibiotics have been recognised as the principle driver of antibiotic resistance. Thus, use of long term antibiotics must be backed with adequate evidence, where the potential benefits outweigh the risks (Edlin et al. 2013).

Evaluation of available evidence for determining the effectiveness of long term antibiotic therapy for the treatment of urinary tract infections (UTIs): a systematic review.

Evidence based practice/research question:

“Are long-term antibiotics more beneficial, to effectively manage urinary tract infections and inform the clinicians and patients during decision making?”

The PICO framework was used for formulating this question, in relation to evidence based practice. This framework facilitated the framing and development of the clinical research question and effectively assisted in adopting certain literature search strategies (Hastings and Fisher 2014). The acronym for the research question are given below:

P- Patients with urinary tract infection

I-  Long term antibiotic therapy

C- None

O- Enhanced health outcomes and reduced symptoms

Research aim- To explore available evidence regarding the administration of long term antibiotic therapy, in people who have been clinically diagnosed with UTI.

Research objectives-

• To explore the impact of long term antibiotic therapy on symptoms of UTI
• To determine the effect of long term antibiotic therapy on frailty and multimorbidity
• To explore the effect of long term antibiotic therapy on patient satisfaction and user experience
• Make recommendations for changes in UTI treatment

Urinary tract infections and subsequently recurrent UTIs, are over diagnosed in the elderly. Thus, antibiotic prophylaxis might essentially be approved for indications that characterise bladder dysfunction or restricted vaginal signs, in place of exact UTI, and therefore might not be able to exert the intended benefits. Infirmity, multimorbidity, and poly-pharmacy are quite prevalent in elder individuals and are influential factors for probable damages, such as, those associated to drug interactions (Martín-Gutiérrez et al. 2015). In addition, older adults who have been prescribed with trimethoprim-containing antibiotics and renin–angiotensin system inhibitors have been found to stay at an increased likelihood of the onset of hyperkalaemia, associated hospitalisation rates, and sudden death (Fralick et al. 2014).

The bacteria that are responsible for UTI are found to enter the urinary bladder through the urethra. However, these infections also occur due to lymph and blood. There is mounting evidence for the fact that females are placed at a greater risk for developing UTI due to their anatomy (Foxman 2013). Antibiotic resistance refers to the capability of microbes to resist the impacts of certain medication that has the potential to successfully kill the microbe. Resistant microbes are often difficult to treat, and thus require high dosage of antimicrobial and/or alternative medications (Niranjan and Malini 2014). These approaches are often more expensive and have toxic impacts on the body of the UTI patients. The resistance to antibiotics often arise due to three different mechanisms namely, genetic mechanisms, natural resistance, or acquiring it from others (Bryce et al. 2016). Thus, microbes that are resistant to several antimicrobials are referred to as multidrug resistant (MDR).

Long-term Antibiotic Therapy for Urinary Tract Infections

A scoping search strategy of several academic databases that are associated with life science and medicine including MEDLINE, CINAHL, and PubMed was conducted. These electronic search engines and databases were fed with key phrases and search terms that were relevant to the phenomenon being investigated (Aveyard 2014). The search was conducted in order to extract relevant evidences from already existing scholarly literature, in order to draw significant conclusions to the research question. The search terms comprised of medical subject headings and keywords that contained information on urinary tract infection and long term antibiotic use.

Publications that combined obtainable evidences in a methodical way, all research designs and confirmation syntheses such as, reviews with overt search procedure that were published internationally, were encompassed in the review. Nonetheless, articles that were published in foreign languages and not English were barred. Also omitted were scholarly literature that establish the grade of 4 (Schünemann et al. 2016). Hence, research that were inconsistent in their findings, and failed to provide detailed beneficial evidence were eliminated from the review. Articles discussed in certain systematic reviews were not involved autonomously in this assessment. However, systematic reviews were contained within this assessment.

Number	Search terms
2	urinary tract Infection AND antibiotics
4	UTI AND antibiotics
5	UTI AND anti-bacterial agent
6	urinary tract infection AND anit-bacterial agent

Table 1- Search strategy

Following input of the search terms, a total of 56 articles were extracted. The duplicates were removed from the databases. This was followed by exclusion of articles after screening their abstracts and titles. The potentially relevant articles were later on identified for assessing their full text eligibility. This led to exclusion of several articles and ultimately resulted in five articles. The inclusion and exclusion criteria for selection of the articles are mentioned below:

Criteria	Population	Intervention	Impact
Inclusion	Humans	· Antibiotic therapy for prolonged period of time · Antibiotic therapy for bacteriuria · Anti-bacterial treatment for UTI	· Health improvement · Health outcome · Satisfaction · Experience · Reduced hospitalisation · Reduced frailty
Exclusion	· Animal models · Clinical guidelines	–	· No measures of healthy outcome · No improvement

Table 2- Inclusion and exclusion criteria

Milestone	Week 1	Week 2	Week 3	Week 4	Week 5	Week 6	Week 7	Week 8
Draft chapter 1 (Introduction)
Draft chapter 2 (Methods)
Evidence search
Critical appraisal
Draft chapter 3 (Results)
Draft chapter 4 (Discussion)

Table 3- Key milestones

The GRADE method refers to a systematic approach that is generally employed for rating the inevitability of confirmation in systematic evaluations and other substantiation syntheses. For the purpose of conducting systematic reviews, the GRADE approach was used owing to the fact that it defines the eminence of a form of evidence as the degree to which one can be assured that an approximation of consequence or connotation is near the amount of specific attention. Quality of the available body of evidence includes reflexion of within-study threat of bias in procedural quality, openness of confirmation, heterogeneity, risk of publication bias, and exactness of effect approximations. The GRADE approach was selected since it stipulates four stages of quality. The maximum quality score is for randomized controlled trials. However, the randomised controlled trials are also given moderate, low and very low ratings based on absence of certain parameters. Some of the common factors that lead to downgrading of the collected evidences are namely, (1) risk of bias, (2) inconsistency between studies, (3) indirectness of results, and (4) serious imprecision. Nonetheless, few studies were also upgraded based on the presence of (1) great effect size, (2) confounding factor adjustment, (3) dose dependent gradient, and (4) confounding show spurious impact, but original results do not show any impact. The table provided below illustrates the GRADE approach that was adopted for appraising the studies.

Underlying method	Quality
Randomised controlled trials; double-upgraded observational studies; superior quality systematic review and/or meta-analysis	High
Systematic review and/or evidence synthesis; downgraded randomized controlled trials; upgraded Observational or survey based studies.	Moderate
Mini reviews; double-downgraded randomized controlled trials; Observational or survey studies or service evaluation.	Low
Expert opinion paper and consensus; triple-downgraded randomized controlled trials; downgraded Observational or survey studies; case series or case reports.	Very low

Research Question and Objectives

Table 4- GRADE scores

The collected information will be presented in a narrative format, where the heterogenous data will be summarised into a table. This will be followed by a thematic analysis of articles. Thematic analysis is one of the most commonly utilised procedures of data analysis in research that is founded on a qualitative design. The thematic analysis will primarily examine, pinpoint, and record different patterns of information and data that will be gathered from the evidences obtained after an exhaustive search of articles. These themes can be defined as specific information code across the extracted scholarly datasets that are crucial for the explanation of the phenomenon being investigated (UTI and long term antibiotic therapy), associated with the research aims and objectives.  It is ultimate that the theme might occur frequent times crossways the scientific articles. Nonetheless, a greater frequency does not unavoidably signify that the theme is more significant to gaining a sound understanding of the research aims and objectives.  

Semantic themes have been found imperative in the identification of the obvious and apparent denotations of the collected information. Hence, this systematic review will comprise of semantic themes that will organise information from scientific articles in a specific pattern to address all the aims and objectives. Although there exists less guidance on the appropriate sample size that is required for conducting a thematic analysis, few evidences consider the number ranging from 6-400 above, based on the data collection method and project size. Thus, less sample size (4 articles) might act as a potential source of bias in this research, owing to the fact that less sample size will prevent generalizability of the results.  Following the thematic analysis, the main findings from the articles shall be written and disseminated, for implementation in evidence based practice.

No.	Author, year	Study type	Population	Intervention type	Outcome	Comments
1	Williams and Craig (2011)	Systematic review	Articles that were selected without any specific language restriction in databases namely, CENTRAL, Cochrane Renal Group’s Specialised Register, EMBASE, and MEDLINE.	Randomised assessments of antibiotics with placebo, new antibiotics, and no treatment for preventing recurrent UTI.	Long term antibiotics were able to reduce the risks related to recurrent and symptomatic urinary tract infection, in among patients	Although long term use of antibiotics were able to reduce recurrent UTI risks, the benefits were not quite large3.
2	Bleidorn et al. (2010)	Randomised controlled trial	80 healthy females aged 18-85 years with at least UTI symptoms	Ciprofloxacin 2 × 250 mg (+1 placebo) oral, or Ibuprofen 3 × 400 mg oral or both together for three days.	21/36 (58.3%) patients administered ibuprofen were symptom free, in comparison to 17/33 (51.5%) patients who were administered ciprofloxacin. Day 4 results demonstrated less symptoms in the total sum score (1; SD 1,42) in ibuprofen patients. Of 58 non-serious adverse effects, 32 were in ibuprofen group, and 26 in ciprofloxacin group.	Although the results demonstrated non-inferiority of ibuprofen, i8n comparison to ciprofloxacin, further trials are required for confirming the results.
3	Beerepoot, Ter Riet and (2012)	Randomised controlled trial	252 post-menopausal females reporting recurrent UTI	12 months prophylaxis with trimethoprim-sulfamethoxazole (480 mg) once daily. Oral capsules with 109 Lactobacillus rhamnosus GR-1 colony forming units and Lactobacillus reuteri RC-14 (twice daily)	Mean number of suggestive UTIs was 2.9 and 3.3 in trimethoprim-sulfamethoxazole and lactobacilli group, after 12months. Minimum of 1 symptomatic UTI was found to occur in 79.1% and 69.3%  of lactobacilli and trimethoprimsulfamethoxazole participants, respectively. Resistance among the participants was not found to increase during lactobacilli prophylaxis	Although L reuteri RC-14 L rhamnosus GR-1 failed to meet the non-inferiority criteria for averting UTIs, in comparison with trimethoprim-sulfamethoxazole, they did not increase antibiotic resistance.
4	Kranj?ec, Papeš and Altarac (2014)	Randomised controlled trial	308 females with reports of recurrent UTI	103 females were subjected to D-mannose powder (2g) prophylaxis daily in 200 ml water for six months. 103 females were daily administered Nitrofurantoin (50 mg).  The other 102 did not get any prophylaxis.	31.8% (98 females) manifested recurrent UTI. Of them 15 were in the  d-mannose group (14.6%), 62 in no prophylaxis group (60.8%), and 21 in the Nitrofurantoin group (20.4%). Reduced risks of recurrent UTI episode were observed in prophylactic group, in comparison to those who had not been subjected to prophylaxis (RR 0.239 and 0.335, P < 0.0001). Lower risk of adverse effects were found in the d-mannose group, in comparison to Nitrofurantoin (RR 0.276, P < 0.0001).	D-mannose was found to significantly lower risks of recurrent UTI, and did not show any difference with the  Nitrofurantoin group. Nonetheless, more tirals are required to establish the findings.

Table 5- Summary of evidences

References

Aveyard, H., 2014. Doing a literature review in health and social care: A practical guide. McGraw-Hill Education (UK).

Beerepoot, M., Ter Riet, G. and Nys, S., 2012. Lactobacilli versus antibiotics to prevent urinary tract infections. A randomized double-blind non-inferiority trial in postmenopausal women. Arch Int Med, 172, pp.704-12.

Bleidorn, J., Gágyor, I., Kochen, M.M., Wegscheider, K. and Hummers-Pradier, E., 2010. Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection?-results of a randomized controlled pilot trial. BMC medicine, 8(1), p.30.

Bryce, A., Hay, A.D., Lane, I.F., Thornton, H.V., Wootton, M. and Costelloe, C., 2016. Global prevalence of antibiotic resistance in paediatric urinary tract infections caused by Escherichia coli and association with routine use of antibiotics in primary care: systematic review and meta-analysis. bmj, 352, p.i939.

Edlin, R.S., Shapiro, D.J., Hersh, A.L. and Copp, H.L., 2013. Antibiotic resistance patterns of outpatient pediatric urinary tract infections. The Journal of urology, 190(1), pp.222-227.

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.

Foxman, B., 2013. Urinary tract infection. In Women and Health (Second Edition) (pp. 553-564).

Foxman, B., 2014. Urinary tract infection syndromes: occurrence, recurrence, bacteriology, risk factors, and disease burden. Infectious disease clinics of North America, 28(1), pp.1-13.

Fralick, M., Macdonald, E.M., Gomes, T., Antoniou, T., Hollands, S., Mamdani, M.M. and Juurlink, D.N., 2014. Co-trimoxazole and sudden death in patients receiving inhibitors of renin-angiotensin system: population based study. Bmj, 349, p.g6196.

Hastings, C. and Fisher, C.A., 2014. Searching for proof: Creating and using an actionable PICO question. Nursing management, 45(8), pp.9-12.

Kranj?ec, B., Papeš, D. and Altarac, S., 2014. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World journal of urology, 32(1), pp.79-84.

Martín-Gutiérrez, G., Porras-González, A., Martín-Pérez, C., Lepe, J.A. and Aznar, J., 2015. Evaluation and optimization of the Sysmex UF1000i system for the screening of urinary tract infection in primary health care elderly patients. Enfermedades infecciosas y microbiologia clinica, 33(5), pp.320-323.

Niranjan, V. and Malini, A., 2014. Antimicrobial resistance pattern in Escherichia coli causing urinary tract infection among inpatients. The Indian journal of medical research, 139(6), p.945.

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.

Schünemann, H.J., Mustafa, R., Brozek, J., Santesso, N., Alonso-Coello, P., Guyatt, G., Scholten, R., Langendam, M., Leeflang, M.M., Akl, E.A. and Singh, J.A., 2016. GRADE Guidelines: 16. GRADE evidence to decision frameworks for tests in clinical practice and public health. Journal of clinical epidemiology, 76, pp.89-98.

Williams, G. and Craig, J.C., 2011. Long?term antibiotics for preventing recurrent urinary tract infection in children. Cochrane database of systematic reviews, (3).