Dataset Information

Individualised versus standard duration of antibiotic therapy in children with acute uncomplicated febrile urinary tract infection: a study protocol and statistical analysis plan for a multicentre randomised clinical trial.

ABSTRACT:

Introduction

Febrile urinary tract infection is one of the most common bacterial infections in children. Currently, recommended antibiotic duration is 10 days. However, recent evidence suggests that 90%-95% of children with febrile urinary tract infections are afebrile and clinically improved 48-72 hours after treatment initiation. Accordingly, individualised duration of antibiotic therapy, according to the recovery time, might be more beneficial than current recommendations, but no evidence exists.

Methods and analysis

An open-label randomised clinical trial equally randomising children aged 3 months to 12 years from eight Danish paediatric departments with uncomplicated febrile (≥38°C) urinary tract infection to either individualised or standard duration of antibiotic therapy. Children allocated to individualised duration of antibiotic therapy will terminate antibiotic therapy 3 days after clinical improvement with no fever, flank pain or dysuria. Children allocated to standard duration will receive 10 days of antibiotic therapy. Co-primary outcomes are non-inferiority for recurrent urinary tract infection or death within 28 days after the end of treatment (non-inferiority margin 7.5 percentage points) and superiority for the number of days with antibiotic therapy within 28 days after treatment initiation. Seven other outcomes will also be assessed. A total of 408 participants are needed to detect non-inferiority (one-sided alpha 2.5%; beta 80%).

Ethics and dissemination

This trial has been approved by the Ethics Committee (H-21057310) and the Data Protection Agency (P-2022-68) in Denmark. Regardless of the trial's findings (whether positive, negative or inconclusive), the results will be compiled into one or more manuscripts for publication in international peer-reviewed scientific journals and presented at conferences.

Trial registration number

NCT05301023.

SUBMITTER: Sethi N

PROVIDER: S-EPMC10277096 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Publications

Individualised versus standard duration of antibiotic therapy in children with acute uncomplicated febrile urinary tract infection: a study protocol and statistical analysis plan for a multicentre randomised clinical trial.

Sethi Naqash N Carlsen Emma Louise Malchau ELM Schmidt Ida Maria IM Cortes Dina D Nygaard Ulrikka U Sehested Line Thousig LT

BMJ open 20230609 6

<h4>Introduction</h4>Febrile urinary tract infection is one of the most common bacterial infections in children. Currently, recommended antibiotic duration is 10 days. However, recent evidence suggests that 90%-95% of children with febrile urinary tract infections are afebrile and clinically improved 48-72 hours after treatment initiation. Accordingly, individualised duration of antibiotic therapy, according to the recovery time, might be more beneficial than current recommendations, but no evid ...[more]

PMID: 37295836

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Project description:BackgroundIn adults with febrile urinary tract infection (fUTI), data on optimal treatment duration in patients other than non-pregnant women without comorbidities are lacking.MethodsA randomized placebo-controlled, double-blind, non-inferiority trial among 35 primary care centers and 7 emergency departments of regional hospitals in the Netherlands. Women and men aged ≥ 18 years with a diagnosis of fUTI were randomly assigned to receive antibiotic treatment for 7 or 14 days (the second week being ciprofloxacin 500 mg or placebo orally twice daily). Patients indicated to receive antimicrobial treatment for at least 14 days were excluded from randomization. The primary endpoint was the clinical cure rate through the 10- to 18-day post-treatment visit with preset subgroup analysis including sex. Secondary endpoints were bacteriologic cure rate at 10-18 days post-treatment and clinical cure at 70-84 days post-treatment.ResultsOf 357 patients included, 200 were eligible for randomization; 97 patients were randomly assigned to 7 days and 103 patients to 14 days of treatment. Overall, short-term clinical cure occurred in 85 (90%) patients treated for 7 days and in 94 (95%) of those treated for 14 days (difference -4.5%; 90% CI, -10.7 to 1.7; P non-inferiority = 0.072, non-inferiority not confirmed). In women, clinical cure was 94% and 93% in those treated for 7 and 14 days, respectively (difference 0.9; 90% CI, -6.9 to 8.7, P non-inferiority = 0.011, non-inferiority confirmed) and, in men, this was 86% versus 98% (difference -11.2; 90% CI -20.6 to -1.8, P superiority = 0.025, inferiority confirmed). The bacteriologic cure rate was 93% versus 97% (difference -4.3%; 90% CI, -9.7 to 1.2, P non-inferiority = 0.041) and the long-term clinical cure rate was 92% versus 91% (difference 1.6%; 90% CI, -5.3 to 8.4; P non-inferiority = 0.005) for 7 days versus 14 days of treatment, respectively. In the subgroups of men and women, long-term clinical cure rates met the criteria for non-inferiority, indicating there was no difference in the need for antibiotic retreatment for UTI during 70-84 days follow-up post-treatment.ConclusionsWomen with fUTI can be treated successfully with antibiotics for 7 days. In men, 7 days of antibiotic treatment for fUTI is inferior to 14 days during short-term follow-up but it is non-inferior when looking at longer follow-up.Trial registrationThe study was registered at ClinicalTrials.gov [ NCT00809913 ; December 16, 2008] and trialregister.nl [ NTR1583 ; December 19, 2008].

Project description:BackgroundMost diagnostic tests for acute uncomplicated urinary tract infections (UTIs) have been previously studied in so-called single-test evaluations. In practice, however, clinicians use more than one test in the diagnostic work-up. Since test results carry overlapping information, results from single-test studies may be confounded. The primary objective of the Amsterdam Cystitis/Urinary Tract Infection Study (ACUTIS) is to determine the (additional) diagnostic value of relevant tests from patient history and laboratory investigations, taking into account their mutual dependencies. Consequently, after suitable validation, an easy to use, multivariable diagnostic rule (clinical index) will be derived.MethodsWomen who contact their GP with painful and/or frequent micturition undergo a series of possibly relevant tests, consisting of patient history questions and laboratory investigations. Using urine culture as the reference standard, two multivariable models (diagnostic indices) will be generated: a model which assumes that patients attend the GP surgery and a model based on telephone contact only. Models will be made more robust using the bootstrap. Discrimination will be visualized in high resolution histograms of the posterior UTI probabilities and summarized as 5th, 10th, 25th 50th, 75th, 90th, and 95th centiles of these, Brier score and the area under the receiver operating characteristics curve (ROC) with 95% confidence intervals. Using the regression coefficients of the independent diagnostic indicators, a diagnostic rule will be derived, consisting of an efficient set of tests and their diagnostic values. The course of the presenting complaints is studied using 7-day patient diaries. To learn more about the natural history of UTIs, patients will be offered the opportunity to postpone the use of antibiotics.DiscussionWe expect that our diagnostic rule will allow efficient diagnosis of UTIs, necessitating the collection of diagnostic indicators with proven added value. GPs may use the rule (preferably after suitable validation) to estimate UTI probabilities for women with different combinations of test results. Finally, in a subcohort, an attempt is made to identify which indicators (including antibiotic treatment) are useful to prognosticate recovery from painful and/or frequent micturition.

Project description:ImportanceUncomplicated urinary tract infection (UTI) is a common indication for outpatient antimicrobial therapy. National guidelines for the management of uncomplicated UTI were published in 2011, but the extent to which they align with current practices, patient diversity, and pathogen biology, all of which have evolved greatly in the time since their publication, is not fully known.ObjectiveTo reevaluate the effectiveness and adverse event profile for first-line antibiotics, fluoroquinolones, and oral β-lactams for treating uncomplicated UTI in contemporary clinical practice.Design, setting, and participantsThis retrospective, population-based cohort study used a claims dataset from Independence Blue Cross, which contains inpatient, outpatient, laboratory, and pharmacy claims that occurred between 2012 and 2021, formatted into the Observational Medical Outcomes Partnership (OMOP) common data model. Participants were nonpregnant female individuals aged 18 years or older with a diagnosis of uncomplicated, nonrecurrent UTI at an outpatient setting. Patients must also have been treated with first-line (nitrofurantoin or trimethoprim-sulfamethoxazole), fluoroquinolone (ciprofloxacin, levofloxacin, or ofloxacin), or oral β-lactam (amoxicillin-clavulanate, cefadroxil, or cefpodoxime) antibiotics. Data analysis was performed from November 2021 to August 2024.ExposuresPatients exposed to first-line antibiotics were assigned to the treatment group, and those exposed to fluoroquinolone or β-lactam treatments were assigned to control groups.Main outcomes and measuresThe primary outcome was a composite end point for treatment failure, defined as outpatient or inpatient revisit within 30 days for UTI, pyelonephritis, or sepsis. Secondary outcomes were the risk of 4 common antibiotic-associated adverse events: gastrointestinal symptoms, rash, kidney injury, and Clostridium difficile infection.ResultsThere were 57 585 episodes of UTI among 49 037 female patients (mean [SD] age, 51.7 [20.1]) years), with prescriptions for first-line antibiotics in 35 018 episodes (61%), fluoroquinolones in 21 140 episodes (37%), and β-lactams in 1427 episodes (2%). After adjustment, receipt of first-line therapies was associated with an absolute risk difference of -1.78% (95% CI, -2.37% to -1.06%) for having a revisit for UTI within 30 days of diagnosis vs fluoroquinolones. First-line therapies were associated with an absolute risk difference of -6.40% (95% CI, -10.14% to -3.24%) for 30-day revisit compared with β-lactam antibiotics. Differences in adverse events were similar between all comparators. Results were identical for models built with an automated OMOP feature extraction package.Conclusions and relevanceIn this cohort study of patients with uncomplicated UTI derived from a large regional claims dataset, national treatment guidelines published almost 14 years ago continue to recommend optimal treatments. These results also provide proof-of-principle that automated feature extraction methods for OMOP formatted data can emulate manually curated models, thereby promoting reproducibility and generalizability.

Dataset Information

Individualised versus standard duration of antibiotic therapy in children with acute uncomplicated febrile urinary tract infection: a study protocol and statistical analysis plan for a multicentre randomised clinical trial.

Introduction

Methods and analysis

Ethics and dissemination

Trial registration number

Publications

Individualised versus standard duration of antibiotic therapy in children with acute uncomplicated febrile urinary tract infection: a study protocol and statistical analysis plan for a multicentre randomised clinical trial.

Similar Datasets

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