Tina Møller Sørensen

Point of care susceptibility testing in primary care - does it lead to a more appropriate prescription of antibiotics in patients with uncomplicated urinary tract infections? Protocol for a randomized controlled trial

BackgroundUrinary tract infection (UTI) is a common infection in primary care and is the second leading reason for prescription of antibiotics in Denmark. The diagnosis is often based on symptoms and urine dip-stick, which has limited validity, causing the risk of unnecessary antibiotic prescription. Additionally, with increasing antibiotic resistance, the risk of choosing an antibiotic to which an infecting pathogen is resistant is rising. Combined point-of-care-tests (POCT) for urine culture and susceptibility testing have been developed and validated for primary care, and performing such a test in all patients with suspected UTI in primary care seems rational in order to reduce the use of inappropriate antibiotics. However, the clinical effect of the culture and susceptibility test has not yet been investigated. This study aims to investigate whether POCT urine culture and susceptibility testing decreases the inappropriate use of antibiotics and leads to faster patient recovery.Methods/designRandomized controlled open label trial of two diagnostic approaches. 750 patients with symptoms of uncomplicated UTI, consecutively contacting their general practitioner (GP), randomized to either POCT urine culture and susceptibility testing and targeted treatment or POCT urine culture without susceptibility testing and empirical treatment. Treatment is started when the POCT is read. The two groups are compared with regard to appropriate choice of antibiotics, clinical remission, and microbiological cure rates.DiscussionThe results of this study may provide important evidence to recommend POCT culture and susceptibility testing in all patients with suspected uncomplicated UTI. This could become an additional strategy to fight antibiotic resistance.Trial registrationClinicalTrials.gov NCT02323087.

Effect of antibiotic treatment in canine and feline urinary tract infections: a systematic review.

Urinary tract infection (UTI) is a major reason for antibiotic prescription in small animal practice. Optimal antibiotic treatment strategies have not been established for veterinary species, especially when considering duration of treatment, which is often considerably longer than for human patients with UTI. The aims of this study were (1) to identify and assess evidence related to the efficacy of antibiotic treatment in canine and feline UTIs; and (2) to compare the efficacy of short (<5 days) and standard (≥7 days) duration of antibiotic treatment for canine uncomplicated UTI. An electronic literature search was conducted for publications to 1 May 2014. Fourteen peer-reviewed prospective and controlled studies were retrieved, 10 of which evaluated antibiotic treatment in dogs and four in cats. Of the 14 studies, seven were clinical trials and five of those were randomised controlled trials. Most (12/14) studies were not considered to contribute sufficient evidence to evaluate treatment strategies. There were no clinical studies examining the effect of duration of the same drug. Of the short duration regimens evaluated, the efficacy of 3 day antibiotic therapy with trimethoprim-sulphonamide (females only) or high-dose enrofloxacin in dogs with uncomplicated UTIs was supported by fair evidence, as these treatment strategies were non-inferior to medium duration (10-14 days) therapy with β-lactam antimicrobials. In conclusion, there is little published evidence relating to antibiotic treatment of UTIs in dogs and cats. Well-designed clinical trials focusing on the duration of treatment are warranted to create evidence-based treatment protocols.

Evaluation of different sampling methods and criteria for diagnosing canine urinary tract infection by quantitative bacterial culture

The use of voided urine specimens for bacteriological culture in dogs is discouraged because contamination from external genitalia could lead to misinterpretation of laboratory results. Quantitative culturing and defining significant bacteriuria could increase the usefulness of voided specimens. However, limited evidence exists for the cut-offs currently recommended. The aim of this study was to evaluate the accuracy of current veterinary cut-off values for significant bacteriuria in voided canine urine. A secondary aim was to investigate if accuracy improved when applying qualitative criteria used in humans. Paired urine specimens were collected by both cystocentesis and voiding, and quantitative bacteriological cultures were performed within the same day. Cystocentesis was used as the reference standard with a cut-off for significant bacteriuria of ≥1000 colony forming units (CFU)/mL. Voided specimens were compared to cystocentesis using: (1) the veterinary cut-off of ≥100,000 CFU/mL; and (2) various cut-offs depending on qualitative criteria (sex, clinical signs and complicating factors), adapted from human guidelines. Ninety-four dogs with suspected urinary tract infection (UTI) were included for analysis. The veterinary cut-off yielded an accuracy of 94% with a sensitivity and specificity of 94% (95% confidence intervals [CI] 0.81, 0.99) and 94% (95% CI 0.86, 0.98), respectively. Applying the human guidelines did not improve overall accuracy (89%), and yielded a sensitivity and specificity of 97% (95% CI 0.86, 1.00) and 86% (95% CI 0.77, 0.92), respectively. The veterinary cut-off value of ≥100,000 CFU/mL for voided urine is appropriate for determining significant bacteriuria in the majority of dogs with suspected UTI if specimens are refrigerated and cultured on the day of collection.

Clinical accuracy of point-of-care urine culture in general practice

Abstract Objective: To assess the clinical accuracy (sensitivity (SEN), specificity (SPE), positive predictive value and negative predictive value) of two point-of-care (POC) urine culture tests for the identification of urinary tract infection (UTI) in general practice. Design: Prospective diagnostic accuracy study comparing two index tests (Flexicult™ SSI-Urinary Kit or ID Flexicult™) with a reference standard (urine culture performed in the microbiological department). Setting: General practice in the Copenhagen area patients. Adult female patients consulting their general practitioner with suspected uncomplicated, symptomatic UTI. Main outcome measures: (1) Overall accuracy of POC urine culture in general practice. (2) Individual accuracy of each of the two POC tests in this study. (3) Accuracy of POC urine culture in general practice with enterococci excluded, since enterococci are known to multiply in boric acid used for transportation for the reference standard. (4) Accuracy based on expert reading of photographs of POC urine cultures performed in general practice. Standard culture performed in the microbiological department was used as reference standard for all four measures. Results: Twenty general practices recruited 341 patients with suspected uncomplicated UTI. The overall agreement between index test and reference was 0.76 (CI: 0.71–0.80), SEN 0.88 (CI: 0.83–0.92) and SPE 0.55 (CI: 0.46–0.64). The two POC tests produced similar results individually. Overall agreement with enterococci excluded was 0.82 (0.77–0.86) and agreement between expert readings of photographs and reference results was 0.81 (CI: 0.76–0.85). Conclusions: POC culture used in general practice has high SEN but low SPE. Low SPE could be due to both misinterpretation in general practice and an imperfect reference standard. Registration number: ClinicalTrials.gov NCT02323087.

Cross-sectional survey on the use and impact of the Danish national antibiotic use guidelines for companion animal practice

BackgroundThe Danish antibiotic use guidelines for companion animal practice were published by the Danish Veterinary Association in 2012. Since then, national surveillance data indicate a 10% reduction in the total use of antibiotics for companion animals, particularly a marked reduction in the use of third generation cephalosporins. The aim of the study was to assess if and how the guidelines have impacted diagnostic and antibiotic prescription habits of the users, and to identify user perceived barriers to implementation.ResultsAn online questionnaire was sent to all 882 members of the Danish Small Animal Veterinary Association in October 2015. The survey was completed by 151 veterinarians. Respondents most frequently consulted the recommendations on skin and urinary tract infections (UTI), and users generally reported a high degree of adherence to the recommendations. Sixty-five per cent indicated that the guidelines had influenced their habits in one or more of the areas being investigated, i.e. perioperative use of antibiotics, use of first line antibiotics for the treatment of pyoderma or UTI, and/or use of microbiological diagnostics. Perioperative use of antibiotics for clean surgeries was uncommon, irrespective of whether respondents had consulted the relevant recommendations or not. On the contrary, significant differences in the prescribing habits between guideline users and non-users were observed for pyoderma and UTI, suggesting an impact of the guidelines towards more prudent antimicrobial use. The diagnostic habits were examined in a subgroup of 63 guideline users. Of those, 19 and 39% reported frequent use of culture and susceptibility (C&S) testing prior to treating pyoderma and UTI respectively, whereas 68–84% reported C&S testing in the event of poor response to treatment or recurrence of infections. The main barriers for implementation of therapeutic recommendations were confidence in old prescribing practices and unavailability of recommended drugs. The main barriers for C&S testing were good experience with empiric treatment, and the owners’ financial situation.ConclusionsThe findings suggest a positive influence of the national antibiotic guidelines on prescription patterns among companion animal practitioners in Denmark. Sustained campaign activity is encouraged and should include promotion of bacteriological testing.

Effect of point-of-care susceptibility testing in general practice on appropriate prescription of antibiotics for patients with uncomplicated urinary tract infection: a diagnostic randomised controlled trial

Objectives To investigate the effect of adding point-of-care (POC) susceptibility testing to POC culture on appropriate use of antibiotics as well as clinical and microbiological cure for patients with suspected uncomplicated urinary tract infection (UTI) in general practice. Design Open, individually randomised controlled trial. Setting General practice. Participants Women with suspected uncomplicated UTI, including elderly patients above 65, patients with recurrent UTI and patients with diabetes. The sample size calculation predicted 600 patients were needed. Interventions Flexicult SSI-Urinary Kit was used for POC culture and susceptibility testing and ID Flexicult was used for POC culture only. Main outcome measures Primary outcome: appropriate antibiotic prescribing on the day after consultation defined as either (1) patient with UTI: to prescribe a first-line antibiotic to which the infecting pathogen was susceptible or a second line if a first line could not be used or (2) patient without UTI: not to prescribe an antibiotic. UTI was defined by typical symptoms and significant growth in a reference urine culture performed at one of two external laboratories. Secondary outcomes: clinical cure on day five according to a 7-day symptom diary and microbiological cure on day 14. Logistic regression models taking into account clustering within practices were used for analysis. Results 20 general practices recruited 191 patients for culture and susceptibility testing and 172 for culture only. 63% of the patients had UTI and 12% of these were resistant to the most commonly used antibiotic, pivmecillinam. Patients randomised to culture only received significantly more appropriate treatment (OR: 1.44 (95% CI 1.03 to 1.99), p=0.03). There was no significant difference in clinical or microbiological cure. Conclusions Adding POC susceptibility testing to POC culture did not improve antibiotic prescribing for patients with suspected uncomplicated UTI in general practice. Susceptibility testing should be reserved for patients at high risk of resistance and complications. Trial registration number NCT02323087; Results.

Effects of Diagnostic Work-Up on Medical Decision-Making for Canine Urinary Tract Infection: An Observational Study in Danish Small Animal Practices: Mapping of UTI Diagnosis and Treatment

Background Clinical signs of urinary tract disease in dogs often lead to prescription of antibiotics. Appropriate diagnostic work‐up could optimize treatment and reduce the risk of inappropriate use of antibiotics. Hypothesis/Objectives To describe and evaluate the impact of diagnostic work‐up on decision to treat (DTT) and choice of antibiotic treatment (COT) for dogs presenting with clinical signs of urinary tract disease. Animals One hundred and fifty‐one dogs presenting to 52 Danish veterinary practices. Methods Prospective, observational study. Clinical signs, diagnostic work‐up, and prescriptions were recorded. Urine samples were submitted to a reference laboratory for quantitative bacterial culture (QBC) and susceptibility testing. The laboratory results were used as reference for assessing the appropriateness of DTT and COT. Results In the majority of dogs, veterinarians performed dipstick (99%), microscopic examination of urine (80%) and bacterial culture (56%). Fifty‐one percent of dogs had urinary tract infection (UTI) based on reference QBC. Appropriate DTT was made for 62% of the dogs, while 36% were over‐prescribed and 2% under‐prescribed. Inappropriate use of second‐line agents was found in 57% of the UTI cases. Performing microscopy—but not culture—significantly impacted DTT (P = 0.039) while no difference was seen in COT (P = 0.67). The accuracy of in‐house microscopy and culture were 64.5 and 77%, respectively. Conclusions and Clinical Importance: Over‐prescription of antibiotics was common among dogs with suspected UTI, regardless of the diagnostic work‐up performed. Test inaccuracy under practice conditions and incoherence between diagnostic test results and decision‐making both explained inappropriate and unnecessary use of antibiotics.