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      Antibiotic prescribing for lower UTI in elderly patients in primary care and risk of bloodstream infection: A cohort study using electronic health records in England

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          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Research has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care.

          Methods and findings

          We analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007–2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations.

          A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97–1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09–1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI.

          Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI.

          Conclusions

          In this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients’ risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults.

          Abstract

          In a study of electronic health record data, Laura Shallcross, Patrick Rockenschaub and colleagues investigate the associations between initiation of antibiotic treatment for UTI and blood stream infection and mortality among older adults in England.

          Author summary

          Why was this study done?
          • Urinary tract infections (UTI) are common in older adults and, alongside respiratory infections, account for the majority of antibiotics prescribed in primary care

          • Antibiotics are often prescribed inappropriately for UTI in the elderly, but the need to reduce prescribing must be balanced against the risk of increasing rare but severe outcomes, such as bloodstream infection, if antibiotic treatment is delayed

          • A recent study in patients aged >65 years found that those who did not receive immediate antibiotic treatment for UTI were more likely to develop bloodstream infection

          What did the researchers do and find?
          • We reanalyzed the relationship between the timing of antibiotic prescribing for UTI and subsequent risk of bloodstream infection (BSI) using the same dataset

          • We did not find evidence to suggest that not immediately prescribing antibiotics for UTI increased a patient’s risk of bloodstream infection, but we did find some evidence of increased mortality.

          • Women were less likely to develop BSI compared with men (adjusted odds ratio [aOR] 0.49, 95% confidence interval [CI] 0.43–0.55, p-value < 0.001). Increasing age (aOR 1.22, 95% CI 1.18–1.27 per 5 years, p-value < 0.001) and social deprivation (Q5 versus Q1: aOR 1.45; 95% CI 1.19–1.76, p-value < 0.001) were also independently associated with BSI.

          • Systematic differences between patients who were/were not treated immediately with antibiotics (residual confounding) remains a potential explanation for our findings in relation to mortality.

          What do these findings mean?
          • This population-based study highlights uncertainty around whether delaying antibiotics in older adults with suspected UTI increases their risk of adverse outcomes.

          • The reasons for the systematic differences identified between patients who were and were not treated immediately with antibiotics warrants further study.

          • Adverse consequences of antibiotic treatment in this population and the public health need to tackle antibiotic resistance highlight the need for novel diagnostic and/or risk prediction strategies to guide antibiotic prescribing decisions for suspected UTI.

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          Most cited references 20

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          The urine dipstick test useful to rule out infections. A meta-analysis of the accuracy

          Background Many studies have evaluated the accuracy of dipstick tests as rapid detectors of bacteriuria and urinary tract infections (UTI). The lack of an adequate explanation for the heterogeneity of the dipstick accuracy stimulates an ongoing debate. The objective of the present meta-analysis was to summarise the available evidence on the diagnostic accuracy of the urine dipstick test, taking into account various pre-defined potential sources of heterogeneity. Methods Literature from 1990 through 1999 was searched in Medline and Embase, and by reference tracking. Selected publications should be concerned with the diagnosis of bacteriuria or urinary tract infections, investigate the use of dipstick tests for nitrites and/or leukocyte esterase, and present empirical data. A checklist was used to assess methodological quality. Results 70 publications were included. Accuracy of nitrites was high in pregnant women (Diagnostic Odds Ratio = 165) and elderly people (DOR = 108). Positive predictive values were ≥80% in elderly and in family medicine. Accuracy of leukocyte-esterase was high in studies in urology patients (DOR = 276). Sensitivities were highest in family medicine (86%). Negative predictive values were high in both tests in all patient groups and settings, except for in family medicine. The combination of both test results showed an important increase in sensitivity. Accuracy was high in studies in urology patients (DOR = 52), in children (DOR = 46), and if clinical information was present (DOR = 28). Sensitivity was highest in studies carried out in family medicine (90%). Predictive values of combinations of positive test results were low in all other situations. Conclusions Overall, this review demonstrates that the urine dipstick test alone seems to be useful in all populations to exclude the presence of infection if the results of both nitrites and leukocyte-esterase are negative. Sensitivities of the combination of both tests vary between 68 and 88% in different patient groups, but positive test results have to be confirmed. Although the combination of positive test results is very sensitive in family practice, the usefulness of the dipstick test alone to rule in infection remains doubtful, even with high pre-test probabilities.
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            Antibiotics in primary care in England: which antibiotics are prescribed and for which conditions?

            To analyse antibiotic prescribing behaviour in English primary care with particular regard to which antibiotics are prescribed and for which conditions.
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              Ibuprofen versus fosfomycin for uncomplicated urinary tract infection in women: randomised controlled trial

              Study question Can treatment of the symptoms of uncomplicated urinary tract infection (UTI) with ibuprofen reduce the rate of antibiotic prescriptions without a significant increase in symptoms, recurrences, or complications? Methods Women aged 18-65 with typical symptoms of UTI and without risk factors or complications were recruited in 42 German general practices and randomly assigned to treatment with a single dose of fosfomycin 3 g (n=246; 243 analysed) or ibuprofen 3×400 mg (n=248; 241 analysed) for three days (and the respective placebo dummies in both groups). In both groups additional antibiotic treatment was subsequently prescribed as necessary for persistent, worsening, or recurrent symptoms. The primary endpoints were the number of all courses of antibiotic treatment on days 0-28 (for UTI or other conditions) and burden of symptoms on days 0-7. The symptom score included dysuria, frequency/urgency, and low abdominal pain. Study answer and limitations The 248 women in the ibuprofen group received significantly fewer course of antibiotics, had a significantly higher total burden of symptoms, and more had pyelonephritis. Four serious adverse events occurred that lead to hospital referrals; one of these was potentially related to the trial drug. Results have to be interpreted carefully as they might apply to women with mild to moderate symptoms rather than to all those with an uncomplicated UTI. What this paper adds Two thirds of women with uncomplicated UTI treated symptomatically with ibuprofen recovered without any antibiotics. Initial symptomatic treatment is a possible approach to be discussed with women willing to avoid immediate antibiotics and to accept a somewhat higher burden of symptoms. Funding, competing interests, data sharing German Federal Ministry of Education and Research (BMBF) No 01KG1105. Patient level data are available from the corresponding author. Patient consent was not obtained but the data are anonymised and risk of identification is low. Trial registration No ClinicalTrialGov Identifier NCT01488955.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: MethodologyRole: Writing – original draftRole: Writing – review & editing
                Role: ValidationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: MethodologyRole: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: Academic Editor
                Journal
                PLoS Med
                PLoS Med
                plos
                plosmed
                PLoS Medicine
                Public Library of Science (San Francisco, CA USA )
                1549-1277
                1549-1676
                21 September 2020
                September 2020
                : 17
                : 9
                Affiliations
                [1 ] Institute of Health Informatics, University College London, London, United Kingdom
                [2 ] Department of Primary Care and Population Health, University College London, London, United Kingdom
                [3 ] Institute of Clinical Trials and Methodology, University College London, London, United Kingdom
                [4 ] Institute of Epidemiology & Healthcare, University College London, London, United Kingdom
                University of Southampton, UNITED KINGDOM
                Author notes

                The authors have declared that no competing interests exist.

                Article
                PMEDICINE-D-20-00884
                10.1371/journal.pmed.1003336
                7505443
                32956399
                © 2020 Shallcross et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                Page count
                Figures: 2, Tables: 3, Pages: 18
                Product
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000269, Economic and Social Research Council;
                Award ID: ES/P008321/1
                Funded by: funder-id http://dx.doi.org/10.13039/501100000659, Research Trainees Coordinating Centre;
                Award ID: CS-2016-007
                Award Recipient :
                This work was supported by the Economic and Social Research Council (ES/P008321/1) and by Health Data Research UK, an initiative funded by UK Research and Innovation, Department of Health and Social Care (England) and the devolved administrations, and leading medical research charities. LS was funded by a National Institute for Health Research (NIHR) Clinician Scientist award (CS-2016-007) for this research project. RB was supported by a UKRI Innovation Fellowship funded by the Medical Research Council (Grant No: MR/S003797/1), AH was funded by an NIHR Senior Investigator award for this project. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Antimicrobials
                Antibiotics
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobials
                Antibiotics
                Medicine and Health Sciences
                Urology
                Genitourinary Infections
                Urinary Tract Infections
                Medicine and Health Sciences
                Epidemiology
                Medical Risk Factors
                Medicine and Health Sciences
                Health Care
                Primary Care
                Medicine and Health Sciences
                Clinical Medicine
                Signs and Symptoms
                Sepsis
                Medicine and Health Sciences
                Health Care
                Health Care Facilities
                Hospitals
                Medicine and Health Sciences
                Hematology
                Bloodstream Infections
                Biology and Life Sciences
                Microbiology
                Microbial Control
                Antimicrobial Resistance
                Antibiotic Resistance
                Medicine and Health Sciences
                Pharmacology
                Antimicrobial Resistance
                Antibiotic Resistance
                Custom metadata
                Clinical Practice Research Datalink (CPRD), Hospital Episode Statistics (HES) and Office for National Statistics (ONS) data cannot be directly shared by the researchers but are available directly from CPRD and NHS Digital subject to standard conditions. All statistical code is available from https://github.com/prockenschaub/CPRD_UTI_sepsis_elderly.

                Medicine

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