Background Excessive and inappropriate use of antibiotics is the most important driver of antimic... more Background Excessive and inappropriate use of antibiotics is the most important driver of antimicrobial resistance. The aim of the HAPPY PATIENT project is to evaluate the adaptation of European Union (EU) recommendations on the prudent use of antimicrobials in human health by evaluating the impact of a multifaceted intervention targeting different categories of healthcare professionals (HCPs) on common community-acquired infectious diseases, especially respiratory and urinary tract infections. Methods/design HAPPY PATIENT was initiated in January 2021 and is planned to end in December 2023. The partners of this project include 15 organizations from 9 countries. Diverse HCPs (doctors, nurses, pharmacists, and pharmacy technicians) will be audited by the Audit Project Odense (APO) method before and after an intervention in four different settings: general practice, out of hours services, nursing homes and community pharmacies in four high antibiotic prescribing countries (France, Pol...
Overview of available diagnostic paths. One Health overview of available diagnostic paths for pat... more Overview of available diagnostic paths. One Health overview of available diagnostic paths for patients with suspected urinary tract infection in human and veterinary primary care practices in Denmark
Background: Resistance to the prescribed antibiotic causes a longer duration of symptoms in patie... more Background: Resistance to the prescribed antibiotic causes a longer duration of symptoms in patients with urinary tract infection. Yet, a study found that patients infected with trimethoprim-resistant Escherichia coli (E. coli) had a prolonged duration of symptoms even if treated with an antibiotic to which the strain was susceptible. The purpose of this study was to attempt to reproduce this finding in a different cohort. Methods: We analyzed data from two studies from general practice in the Capital Region of Denmark including patients from 2014 to 2016. The primary outcome was the severity of frequency and dysuria. The secondary outcome was the number of days until symptoms had disappeared. Results: We included 180 women treated for uncomplicated cystitis caused by E. coli. We found that 16.11% (n = 29) of the E. coli strains were resistant to all of the three selected antibiotics (ampicillin, sulfamethizole and trimethoprim). There was no significant difference in severity or ti...
This study was aimed at evaluating the appropriateness of use and interpretation of rapid antigen... more This study was aimed at evaluating the appropriateness of use and interpretation of rapid antigen detection testing (RADT) and antibiotic prescribing for acute pharyngitis six years after a multifaceted intervention. Design: Before-and-after audit-based study. Location: Primary care centres in eight autonomous Communities. Participants: General practitioners (GP) who had participated in the HAPPY AUDIT intervention study in 2008 and 2009 were invited to participate in a third audit-based study six years later (2015). Method: RADTs were provided to the participating practices and the GPs were requested to consecutively register all adults with acute pharyngitis. A registration form specifically designed for this study was used. Results: A total of 121 GPs out of the 210 who participated in the first two audits agreed to participate in the third audit (57.6%). They registered 3394 episodes of pharyngitis in the three registrations. RADTs were used in 51.7% of all the cases immediately after the intervention, and in 49.4% six years later. Antibiotics were prescribed in 21.3% and 36.1%, respectively (P < .
ObjectivesThe aim of this study was to investigate the impact of age on the diagnostic properties... more ObjectivesThe aim of this study was to investigate the impact of age on the diagnostic properties of typical symptoms of urinary tract infection (UTI) in women presenting in general practice with symptoms suggestive of UTI with significant bacteriuria as the reference standard.DesignDiagnostic accuracy study.SettingGeneral practice, Copenhagen, Denmark.ParticipantsAdult 15 years or older. Women presenting in general practice with symptoms suggestive of UTI where urine was collected for investigation.Primary and secondary outcome measuresAccuracy of four symptoms of UTI (dysuria, frequency, urge and abdominal pain) in six different age groups.Results90 practices included 1178 adult women. The prevalence of bacteriuria varied between 30% in women aged 30–44 years and 67% in women aged 75–89 years. The likelihood ratios for dysuria varied between age groups with the best performance in women aged 15–29 (positive likelihood ratio (pLR): 1.62 (1.30–1.94), negative likelihood ratio (nLR):...
Urinary tract infections (UTIs) are common in nursing home (NH) residents and Denmark is one of t... more Urinary tract infections (UTIs) are common in nursing home (NH) residents and Denmark is one of the countries with the highest antibiotic use in NHs. The aim of this study was to assess the quality of the diagnostic process and treatment decision on the day of the first contact from NHs to general practice and assess predictors for prescription of antibiotics in NH residents without an indwelling urinary catheter. The study was a prospective observational study in general practice in the Capital Region of Denmark; 490 patients were included; 158 out of 394 (40.1%, 95% CI 35; 45) patients with suspected UTI had urinary tract symptoms; 270 out of 296 (91.2%, 95% CI 87; 94) patients without urinary tract symptoms had a urine culture performed. Performing urine culture in the general practice was inversely associated to prescription of antibiotics on day one (OR 0.27, 95% CI 0.13; 0.56). It is imperative to support the implementation of interventions aimed at improving the quality of th...
BACKGROUND: To evaluate the effectiveness of short courses of antibiotic therapy for patients wit... more BACKGROUND: To evaluate the effectiveness of short courses of antibiotic therapy for patients with acute streptococcal pharyngitis. METHODS: Randomized controlled trials comparing short-course antibiotic therapy (≤5 days) with long-course antibiotic therapy (≥7 days) for patients with streptococcal pharyngitis were included. Two primary outcomes: early clinical cure and early bacterial eradication. RESULTS: Fifty randomized clinical trials were included. Overall, short-course antibiotic treatment was as effective as long-course antibiotic treatment for early clinical cure (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.79 to 1.15). Subgroup analysis showed that short-course penicillin was less effective for early clinical cure (OR 0.43; 95% CI, 0.23 to 0.82) and bacteriological eradication (OR 0.34; 95% CI, 0.19 to 0.61) in comparison to long-course penicillin. Short-course macrolides were equally effective, compared to long-course penicillin. Finally, short-course cephalospor...
Background: Inappropriate prescription of antibiotics is the leading driver of antimicrobial resi... more Background: Inappropriate prescription of antibiotics is the leading driver of antimicrobial resistance (AMR). The majority of antibiotics are prescribed in primary care. Understanding how general practitioners (GPs) use diagnostic tests and the effect on treatment decision under daily practice conditions is important to reduce inappropriate prescription of antibiotics. The aim of the study was to investigate the use of diagnostic tests in primary care patients with suspected urinary tract infection (UTI) and to assess the appropriateness of the treatment decision (TD) under daily practice conditions in Denmark. Methods: Prospective observational study. Symptomatic adult patients consulting general practice with suspected UTI recruited over 12 months. The diagnostic workup was registered in a standardized form. The appropriateness of the TD was assessed based on the results of a culture performed at a reference microbiological laboratory. TD was considered appropriate if a patient had a positive culture and was prescribed antibiotics or had a negative culture and was not prescribed antibiotics. TD was considered inappropriate if a patient had a negative culture and was prescribed antibiotics (overtreatment) or had a positive culture and was not prescribed antibiotics (undertreatment). Results: Four hundred and eighty-eight patients were included. Dipstick was used in 98% of the patients and urine culture was used in 89% of the patients; 317 had the culture performed in practice and 117 had the culture performed at the hospital. The appropriateness of the final TD was significantly (p = 0.04) lower in patients without culture (55%) than in patients with culture performed in practice (71%) or at hospital (69%). Conclusion: In a context with wide availability of diagnostic tests, GPs use diagnostic tests for the decision-making process in all patients with suspected UTI. Urine culture is used in the majority of the patients and is associated with a higher proportion of appropriate treatment decisions. Performance of urine culture is therefore important in reducing inappropriate antibiotic prescribing in patients with suspected UTI seeking care in general practice in Denmark. Trial registration: ClinicalTrials.gov NCT02249273.
This paper summarises the discussion during the workshop on ‘Overdiagnosis and overtreatment of i... more This paper summarises the discussion during the workshop on ‘Overdiagnosis and overtreatment of infectious diseases in general practice. How and where to break the endless loop?’ The workshop was organised as part of the overdiagnosis conference carried out in August 2018 in Copenhagen, Denmark. During the workshop, participants from all over the world reflected on the challenges of embracing the overdiagnosis paradigm as a tool to advance understanding and to find solutions to the unnecessary use of antibiotics in primary health care. It was concluded that the narrow view of the overdiagnosis paradigm does not provide theoretical resources to address the problem of the inherent connection between diagnostic error and treatment decision. In contrast to the overdiagnosis paradigm, the too much medicine paradigm is an umbrella term suitable to frame actions that recognise the complexity of the decision-making process during the consultation and its impact on overtreatment.
ObjectivesTo investigate the effect of adding point-of-care (POC) susceptibility testing to POC c... more ObjectivesTo 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.DesignOpen, individually randomised controlled trial.SettingGeneral practice.ParticipantsWomen 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.InterventionsFlexicult SSI-Urinary Kit was used for POC culture and susceptibility testing and ID Flexicult was used for POC culture only.Main outcome measuresPrimary 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 witho...
Objective: To assess the clinical accuracy (sensitivity (SEN), specificity (SPE), positive predic... more 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 TM SSI-Urinary Kit or ID Flexicult TM) 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.
Background: The One Health approach is emerging in response to the development of bacterial resis... more Background: The One Health approach is emerging in response to the development of bacterial resistance. To the best of our knowledge, the possibility to use this approach in a clinical context has not yet been explored. Thus, in this paper, we report the procedures to implement a prospective observational study of diagnostic pathways in human and canine patients with suspected urinary tract infection as a means to assess the feasibility and synergistic value of setting up One Health clinical research projects and interventions. Methods/design: A prospective observational study will compare different diagnostic pathways (i.e., 16 possible combinations of diagnostic tools) to gold standard in human and veterinary primary care practice in Denmark. Fifty primary care practices and 100 veterinary clinics will each consecutively include 20 human patients or 8-10 dogs, respectively. Data will be collected at practice and patient level comprising (a) information about the organization of the practice and access to different diagnostic tools, (b) information about clinical history, diagnostic path and treatment during the index consultation, (c) information about severity of symptoms during the 7-10 days following inclusion, and (d) urine culture (type of microorganism and susceptibility test). The feasibility and synergistic value of conducting future research, and/or designing common interventions, will be assessed by evaluating the comparability of human primary care and veterinary primary care with respect to study implementation and study results. Discussion: Results from this study will give an insight into the feasibility and synergistic value of setting-up One Health research projects in a clinical context. This is crucial if we are to embrace the One Health approach, as a legitimate strategy to implement common interventions aimed at influencing the diagnostic process in human and canine patients in order to decrease inappropriate use of antibiotics. Trial registration: The study in humans has been registered in ClinicalTrials.gov NCT02249273.
Background: Urinary tract infection (UTI) is a common infection in primary care and is the second... more Background: Urinary 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 dipstick , 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/design: Randomized 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.
Over-the-counter nitrofurantoin for self diagnosed uncomplicated cystitis should be considered wi... more Over-the-counter nitrofurantoin for self diagnosed uncomplicated cystitis should be considered with caution and may cause more harm than good. 1
The aim of this study was to describe the antibiotic prescribing rate in patients with acute exac... more The aim of this study was to describe the antibiotic prescribing rate in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), to analyse predictors for antibiotic prescribing and to explore the influence of the use C-reactive protein (CRP) rapid test. A cross-sectional study was carried out in January and February 2008 in primary care. General practitioners (GPs) from six countries (Denmark, Sweden, Lithuania, Russia, Spain and Argentina) registered all patients with AECOPD during a 3-week period. A multilevel logistic regression model was estimated using two hierarchical levels, (i) patients and (ii) physicians, and was used to analyse the association between antibiotic prescribing and potential predictors for antibiotic use: patients' age and gender, duration and symptoms and signs of exacerbations (fever, cough, dyspnoea, sputum volume and purulence) and the results of the CRP test. A total of 617 GPs registered 1233 patients with AECOPD. A tota...
Background: Variation in prescription of antibiotics in primary care can indicate poor clinical p... more Background: Variation in prescription of antibiotics in primary care can indicate poor clinical practice that contributes to the increase of resistant strains. General Practitioners (GPs), as a professional group, are expected to have a fairly homogeneous prescribing style. In this paper, we describe variation in prescribing style within and across groups of GPs from six countries. Methods: Cross-sectional study with the inclusion of 457 GPs and 6394 sore throat patients. We describe variation in prescribing antibiotics for sore throat patients across six countries and assess whether variation in "prescribing style"understood as a subjective tendency to prescribehas an important effect on variation in prescription of antibiotics by using the concept of prescribing style as a latent variable in a multivariable model. We report variation as a Median Odds Ratio (MOR) which is the transformation of the random effect variance onto an odds ratio; Thus, MOR = 1 means similar odds or strict homogeneity between GPs' prescribing style, while a MOR higher than 1 denotes heterogeneity in prescribing style. Results: In all countries some GPs always prescribed antibiotics to all their patients, while other GPs never did. After adjusting for patient and GP characteristics, prescribing style in the group of GPs from Russia was about three times more heterogeneous than the prescribing style in the group of GPs from Denmark-Median Odds Ratio (6.8, 95% CI 3.1;8.8) and (2.6, 95% CI 2.2;4.4) respectively. Conclusion: Prescribing style is an important source of variation in prescription of antibiotics within and across countries, even after adjusting for patient and GP characteristics. Interventions aimed at influencing the prescribing style of GPs must encompass context-specific actions at the policy-making level alongside GP-targeted interventions to enable GPs to react more objectively to the external demands that are in place when making the decision of prescribing antibiotics or not.
Atencion primaria / Sociedad Española de Medicina de Familia y Comunitaria, 2014
To evaluate the effectiveness of two types of intervention in reducing antibiotic prescribing in ... more To evaluate the effectiveness of two types of intervention in reducing antibiotic prescribing in respiratory tract infections (RTI). Before-after audit-based study. Primary Care centres in Spain. General practitioners (GPs) registered all patients with RTIs for 15 days in winter 2008 (pre-intervention), and again in winter 2009 (post-intervention). Intervention activities included meetings, with the presentation and discussion of the results, and several training meetings on RTI guidelines, information brochures for patients, workshops on point-of-care tests - rapid antigen detection tests and C-reactive protein rapid test - and provision of these tests in the clinic. All GPs, with the exception of those in Catalonia, made up the full intervention group (FIG); conversely, Catalan doctors underwent the same intervention, except for the workshop on rapid tests (partial intervention group, PIG). Multilevel logistic regression was performed taking the prescription of antibiotics as the ...
Primary care respiratory journal : journal of the General Practice Airways Group, 2013
In patients with lower respiratory tract infections (LRTIs) it is a challenge to identify who sho... more In patients with lower respiratory tract infections (LRTIs) it is a challenge to identify who should be treated with antibiotics. According to international guidelines, antibiotics should be prescribed to patients with suspected pneumonia while acute bronchitis is considered a viral infection and should, generally, not be treated with antibiotics. Overdiagnosis of pneumonia in patients with LRTIs may lead to antibiotic overprescribing. To investigate the prevalence of presumed pneumonia in patients with LRTI in two countries with different antibiotic prescribing rates (Denmark and Spain) and to compare which symptoms and clinical tests are of most importance for the GP when choosing a diagnosis of pneumonia rather than acute bronchitis. A cross-sectional study including GPs from Denmark and Spain was conducted as part of the EU-funded project HAPPY AUDIT. A total of 2,698 patients with LRTI were included. In Denmark, 47% of the patients with LRTI were classified with a diagnosis of ...
Objectives: To obtain detailed information on current prescribing rates of antibiotics for respir... more Objectives: To obtain detailed information on current prescribing rates of antibiotics for respiratory tract infections (RTIs) in Dutch general practice and its relation with age and respiratory tract clinical entities. Methods: We assessed the mean proportion of antibiotics prescribed for RTIs per age group, contactbased and population-based using all patient contacts concerning RTIs in the year 2000 selected from the IPCI database, containing information on general practice consultations of 235 290 patients. Results: In one-third of all contacts concerning RTIs, antibiotics were prescribed, with much variation between age groups and clinical entities. For children (0-15 years) and the elderly (over 75 years), the lowest contact-based percentages of prescribed antibiotics for RTIs were found, while populationbased, children of age 0-5 years received far more antibiotics for RTIs. High prescribing rates were seen in patients with sinusitis-like complaints (67%) or pneumonia (78%), whereas low rates were found for patients with upper RTIs (16%). Conclusions: Potential over-prescribing of antibiotics for RTIs occurs in the age group 31-65 years, not in children and the elderly, and in patients with upper RTIs, sinusitis and most likely acute bronchitis (contact-based). The management of these subgroups of patients should be addressed in quality assurance programmes. Children and the elderly visit the GP much more often than adults, which can be explained by more frequent (children) or more severe (elderly) RTI morbidity, but in proportion they do not receive more antibiotics.
Background: Excessive use of antibiotics is worldwide the most important reason for development o... more Background: Excessive use of antibiotics is worldwide the most important reason for development of antimicrobial resistance. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. Initiatives have been taken to improve the quality of antibiotic prescribing in primary care, but only few studies have been designed to determine the effectiveness of multifaceted strategies across countries with different practice setting. The aim of this study was to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different health organization and different prevalence of antibiotic resistance. Methods: GPs from two Nordic countries, two Baltic Countries and two Hispano-American countries registered patients with respiratory tract infections (RTIs) in 2008 and 2009. After first registration they received individual prescriber feedback and they were offered an intervention programme that included training courses, clinical guidelines, posters for waiting rooms, patient brochures and access to point of care tests (Strep A and C-Reactive Protein). Antibiotic prescribing rates were compared before and after the intervention. Results: A total of 440 GPs registered 47011 consultations; 24436 before the intervention (2008) and 22575 after the intervention (2009). After the intervention, the GPs significantly reduced the percentage of consultations resulting in an antibiotic prescription. In patients with lower RTI the GPs in Lithuania reduced the prescribing rate by 42%, in Russia by 25%, in Spain by 25%, and in Argentina by 9%. In patients with upper RTIs, the corresponding reductions in the antibiotic prescribing rates were in Lithania 20%, in Russia 15%, in Spain 9%, and in Argentina 5%. Conclusion: A multifaceted intervention programme targeting GPs and patients and focusing on improving diagnostic procedures in patients with RTIs may lead to a marked reduction in antibiotic prescribing. The pragmatic before-after design used may suffer from some limitations and the reduction in antibiotic prescribing could be influenced by factors not related to the intervention.
Background Excessive and inappropriate use of antibiotics is the most important driver of antimic... more Background Excessive and inappropriate use of antibiotics is the most important driver of antimicrobial resistance. The aim of the HAPPY PATIENT project is to evaluate the adaptation of European Union (EU) recommendations on the prudent use of antimicrobials in human health by evaluating the impact of a multifaceted intervention targeting different categories of healthcare professionals (HCPs) on common community-acquired infectious diseases, especially respiratory and urinary tract infections. Methods/design HAPPY PATIENT was initiated in January 2021 and is planned to end in December 2023. The partners of this project include 15 organizations from 9 countries. Diverse HCPs (doctors, nurses, pharmacists, and pharmacy technicians) will be audited by the Audit Project Odense (APO) method before and after an intervention in four different settings: general practice, out of hours services, nursing homes and community pharmacies in four high antibiotic prescribing countries (France, Pol...
Overview of available diagnostic paths. One Health overview of available diagnostic paths for pat... more Overview of available diagnostic paths. One Health overview of available diagnostic paths for patients with suspected urinary tract infection in human and veterinary primary care practices in Denmark
Background: Resistance to the prescribed antibiotic causes a longer duration of symptoms in patie... more Background: Resistance to the prescribed antibiotic causes a longer duration of symptoms in patients with urinary tract infection. Yet, a study found that patients infected with trimethoprim-resistant Escherichia coli (E. coli) had a prolonged duration of symptoms even if treated with an antibiotic to which the strain was susceptible. The purpose of this study was to attempt to reproduce this finding in a different cohort. Methods: We analyzed data from two studies from general practice in the Capital Region of Denmark including patients from 2014 to 2016. The primary outcome was the severity of frequency and dysuria. The secondary outcome was the number of days until symptoms had disappeared. Results: We included 180 women treated for uncomplicated cystitis caused by E. coli. We found that 16.11% (n = 29) of the E. coli strains were resistant to all of the three selected antibiotics (ampicillin, sulfamethizole and trimethoprim). There was no significant difference in severity or ti...
This study was aimed at evaluating the appropriateness of use and interpretation of rapid antigen... more This study was aimed at evaluating the appropriateness of use and interpretation of rapid antigen detection testing (RADT) and antibiotic prescribing for acute pharyngitis six years after a multifaceted intervention. Design: Before-and-after audit-based study. Location: Primary care centres in eight autonomous Communities. Participants: General practitioners (GP) who had participated in the HAPPY AUDIT intervention study in 2008 and 2009 were invited to participate in a third audit-based study six years later (2015). Method: RADTs were provided to the participating practices and the GPs were requested to consecutively register all adults with acute pharyngitis. A registration form specifically designed for this study was used. Results: A total of 121 GPs out of the 210 who participated in the first two audits agreed to participate in the third audit (57.6%). They registered 3394 episodes of pharyngitis in the three registrations. RADTs were used in 51.7% of all the cases immediately after the intervention, and in 49.4% six years later. Antibiotics were prescribed in 21.3% and 36.1%, respectively (P < .
ObjectivesThe aim of this study was to investigate the impact of age on the diagnostic properties... more ObjectivesThe aim of this study was to investigate the impact of age on the diagnostic properties of typical symptoms of urinary tract infection (UTI) in women presenting in general practice with symptoms suggestive of UTI with significant bacteriuria as the reference standard.DesignDiagnostic accuracy study.SettingGeneral practice, Copenhagen, Denmark.ParticipantsAdult 15 years or older. Women presenting in general practice with symptoms suggestive of UTI where urine was collected for investigation.Primary and secondary outcome measuresAccuracy of four symptoms of UTI (dysuria, frequency, urge and abdominal pain) in six different age groups.Results90 practices included 1178 adult women. The prevalence of bacteriuria varied between 30% in women aged 30–44 years and 67% in women aged 75–89 years. The likelihood ratios for dysuria varied between age groups with the best performance in women aged 15–29 (positive likelihood ratio (pLR): 1.62 (1.30–1.94), negative likelihood ratio (nLR):...
Urinary tract infections (UTIs) are common in nursing home (NH) residents and Denmark is one of t... more Urinary tract infections (UTIs) are common in nursing home (NH) residents and Denmark is one of the countries with the highest antibiotic use in NHs. The aim of this study was to assess the quality of the diagnostic process and treatment decision on the day of the first contact from NHs to general practice and assess predictors for prescription of antibiotics in NH residents without an indwelling urinary catheter. The study was a prospective observational study in general practice in the Capital Region of Denmark; 490 patients were included; 158 out of 394 (40.1%, 95% CI 35; 45) patients with suspected UTI had urinary tract symptoms; 270 out of 296 (91.2%, 95% CI 87; 94) patients without urinary tract symptoms had a urine culture performed. Performing urine culture in the general practice was inversely associated to prescription of antibiotics on day one (OR 0.27, 95% CI 0.13; 0.56). It is imperative to support the implementation of interventions aimed at improving the quality of th...
BACKGROUND: To evaluate the effectiveness of short courses of antibiotic therapy for patients wit... more BACKGROUND: To evaluate the effectiveness of short courses of antibiotic therapy for patients with acute streptococcal pharyngitis. METHODS: Randomized controlled trials comparing short-course antibiotic therapy (≤5 days) with long-course antibiotic therapy (≥7 days) for patients with streptococcal pharyngitis were included. Two primary outcomes: early clinical cure and early bacterial eradication. RESULTS: Fifty randomized clinical trials were included. Overall, short-course antibiotic treatment was as effective as long-course antibiotic treatment for early clinical cure (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.79 to 1.15). Subgroup analysis showed that short-course penicillin was less effective for early clinical cure (OR 0.43; 95% CI, 0.23 to 0.82) and bacteriological eradication (OR 0.34; 95% CI, 0.19 to 0.61) in comparison to long-course penicillin. Short-course macrolides were equally effective, compared to long-course penicillin. Finally, short-course cephalospor...
Background: Inappropriate prescription of antibiotics is the leading driver of antimicrobial resi... more Background: Inappropriate prescription of antibiotics is the leading driver of antimicrobial resistance (AMR). The majority of antibiotics are prescribed in primary care. Understanding how general practitioners (GPs) use diagnostic tests and the effect on treatment decision under daily practice conditions is important to reduce inappropriate prescription of antibiotics. The aim of the study was to investigate the use of diagnostic tests in primary care patients with suspected urinary tract infection (UTI) and to assess the appropriateness of the treatment decision (TD) under daily practice conditions in Denmark. Methods: Prospective observational study. Symptomatic adult patients consulting general practice with suspected UTI recruited over 12 months. The diagnostic workup was registered in a standardized form. The appropriateness of the TD was assessed based on the results of a culture performed at a reference microbiological laboratory. TD was considered appropriate if a patient had a positive culture and was prescribed antibiotics or had a negative culture and was not prescribed antibiotics. TD was considered inappropriate if a patient had a negative culture and was prescribed antibiotics (overtreatment) or had a positive culture and was not prescribed antibiotics (undertreatment). Results: Four hundred and eighty-eight patients were included. Dipstick was used in 98% of the patients and urine culture was used in 89% of the patients; 317 had the culture performed in practice and 117 had the culture performed at the hospital. The appropriateness of the final TD was significantly (p = 0.04) lower in patients without culture (55%) than in patients with culture performed in practice (71%) or at hospital (69%). Conclusion: In a context with wide availability of diagnostic tests, GPs use diagnostic tests for the decision-making process in all patients with suspected UTI. Urine culture is used in the majority of the patients and is associated with a higher proportion of appropriate treatment decisions. Performance of urine culture is therefore important in reducing inappropriate antibiotic prescribing in patients with suspected UTI seeking care in general practice in Denmark. Trial registration: ClinicalTrials.gov NCT02249273.
This paper summarises the discussion during the workshop on ‘Overdiagnosis and overtreatment of i... more This paper summarises the discussion during the workshop on ‘Overdiagnosis and overtreatment of infectious diseases in general practice. How and where to break the endless loop?’ The workshop was organised as part of the overdiagnosis conference carried out in August 2018 in Copenhagen, Denmark. During the workshop, participants from all over the world reflected on the challenges of embracing the overdiagnosis paradigm as a tool to advance understanding and to find solutions to the unnecessary use of antibiotics in primary health care. It was concluded that the narrow view of the overdiagnosis paradigm does not provide theoretical resources to address the problem of the inherent connection between diagnostic error and treatment decision. In contrast to the overdiagnosis paradigm, the too much medicine paradigm is an umbrella term suitable to frame actions that recognise the complexity of the decision-making process during the consultation and its impact on overtreatment.
ObjectivesTo investigate the effect of adding point-of-care (POC) susceptibility testing to POC c... more ObjectivesTo 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.DesignOpen, individually randomised controlled trial.SettingGeneral practice.ParticipantsWomen 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.InterventionsFlexicult SSI-Urinary Kit was used for POC culture and susceptibility testing and ID Flexicult was used for POC culture only.Main outcome measuresPrimary 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 witho...
Objective: To assess the clinical accuracy (sensitivity (SEN), specificity (SPE), positive predic... more 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 TM SSI-Urinary Kit or ID Flexicult TM) 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.
Background: The One Health approach is emerging in response to the development of bacterial resis... more Background: The One Health approach is emerging in response to the development of bacterial resistance. To the best of our knowledge, the possibility to use this approach in a clinical context has not yet been explored. Thus, in this paper, we report the procedures to implement a prospective observational study of diagnostic pathways in human and canine patients with suspected urinary tract infection as a means to assess the feasibility and synergistic value of setting up One Health clinical research projects and interventions. Methods/design: A prospective observational study will compare different diagnostic pathways (i.e., 16 possible combinations of diagnostic tools) to gold standard in human and veterinary primary care practice in Denmark. Fifty primary care practices and 100 veterinary clinics will each consecutively include 20 human patients or 8-10 dogs, respectively. Data will be collected at practice and patient level comprising (a) information about the organization of the practice and access to different diagnostic tools, (b) information about clinical history, diagnostic path and treatment during the index consultation, (c) information about severity of symptoms during the 7-10 days following inclusion, and (d) urine culture (type of microorganism and susceptibility test). The feasibility and synergistic value of conducting future research, and/or designing common interventions, will be assessed by evaluating the comparability of human primary care and veterinary primary care with respect to study implementation and study results. Discussion: Results from this study will give an insight into the feasibility and synergistic value of setting-up One Health research projects in a clinical context. This is crucial if we are to embrace the One Health approach, as a legitimate strategy to implement common interventions aimed at influencing the diagnostic process in human and canine patients in order to decrease inappropriate use of antibiotics. Trial registration: The study in humans has been registered in ClinicalTrials.gov NCT02249273.
Background: Urinary tract infection (UTI) is a common infection in primary care and is the second... more Background: Urinary 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 dipstick , 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/design: Randomized 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.
Over-the-counter nitrofurantoin for self diagnosed uncomplicated cystitis should be considered wi... more Over-the-counter nitrofurantoin for self diagnosed uncomplicated cystitis should be considered with caution and may cause more harm than good. 1
The aim of this study was to describe the antibiotic prescribing rate in patients with acute exac... more The aim of this study was to describe the antibiotic prescribing rate in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), to analyse predictors for antibiotic prescribing and to explore the influence of the use C-reactive protein (CRP) rapid test. A cross-sectional study was carried out in January and February 2008 in primary care. General practitioners (GPs) from six countries (Denmark, Sweden, Lithuania, Russia, Spain and Argentina) registered all patients with AECOPD during a 3-week period. A multilevel logistic regression model was estimated using two hierarchical levels, (i) patients and (ii) physicians, and was used to analyse the association between antibiotic prescribing and potential predictors for antibiotic use: patients' age and gender, duration and symptoms and signs of exacerbations (fever, cough, dyspnoea, sputum volume and purulence) and the results of the CRP test. A total of 617 GPs registered 1233 patients with AECOPD. A tota...
Background: Variation in prescription of antibiotics in primary care can indicate poor clinical p... more Background: Variation in prescription of antibiotics in primary care can indicate poor clinical practice that contributes to the increase of resistant strains. General Practitioners (GPs), as a professional group, are expected to have a fairly homogeneous prescribing style. In this paper, we describe variation in prescribing style within and across groups of GPs from six countries. Methods: Cross-sectional study with the inclusion of 457 GPs and 6394 sore throat patients. We describe variation in prescribing antibiotics for sore throat patients across six countries and assess whether variation in "prescribing style"understood as a subjective tendency to prescribehas an important effect on variation in prescription of antibiotics by using the concept of prescribing style as a latent variable in a multivariable model. We report variation as a Median Odds Ratio (MOR) which is the transformation of the random effect variance onto an odds ratio; Thus, MOR = 1 means similar odds or strict homogeneity between GPs' prescribing style, while a MOR higher than 1 denotes heterogeneity in prescribing style. Results: In all countries some GPs always prescribed antibiotics to all their patients, while other GPs never did. After adjusting for patient and GP characteristics, prescribing style in the group of GPs from Russia was about three times more heterogeneous than the prescribing style in the group of GPs from Denmark-Median Odds Ratio (6.8, 95% CI 3.1;8.8) and (2.6, 95% CI 2.2;4.4) respectively. Conclusion: Prescribing style is an important source of variation in prescription of antibiotics within and across countries, even after adjusting for patient and GP characteristics. Interventions aimed at influencing the prescribing style of GPs must encompass context-specific actions at the policy-making level alongside GP-targeted interventions to enable GPs to react more objectively to the external demands that are in place when making the decision of prescribing antibiotics or not.
Atencion primaria / Sociedad Española de Medicina de Familia y Comunitaria, 2014
To evaluate the effectiveness of two types of intervention in reducing antibiotic prescribing in ... more To evaluate the effectiveness of two types of intervention in reducing antibiotic prescribing in respiratory tract infections (RTI). Before-after audit-based study. Primary Care centres in Spain. General practitioners (GPs) registered all patients with RTIs for 15 days in winter 2008 (pre-intervention), and again in winter 2009 (post-intervention). Intervention activities included meetings, with the presentation and discussion of the results, and several training meetings on RTI guidelines, information brochures for patients, workshops on point-of-care tests - rapid antigen detection tests and C-reactive protein rapid test - and provision of these tests in the clinic. All GPs, with the exception of those in Catalonia, made up the full intervention group (FIG); conversely, Catalan doctors underwent the same intervention, except for the workshop on rapid tests (partial intervention group, PIG). Multilevel logistic regression was performed taking the prescription of antibiotics as the ...
Primary care respiratory journal : journal of the General Practice Airways Group, 2013
In patients with lower respiratory tract infections (LRTIs) it is a challenge to identify who sho... more In patients with lower respiratory tract infections (LRTIs) it is a challenge to identify who should be treated with antibiotics. According to international guidelines, antibiotics should be prescribed to patients with suspected pneumonia while acute bronchitis is considered a viral infection and should, generally, not be treated with antibiotics. Overdiagnosis of pneumonia in patients with LRTIs may lead to antibiotic overprescribing. To investigate the prevalence of presumed pneumonia in patients with LRTI in two countries with different antibiotic prescribing rates (Denmark and Spain) and to compare which symptoms and clinical tests are of most importance for the GP when choosing a diagnosis of pneumonia rather than acute bronchitis. A cross-sectional study including GPs from Denmark and Spain was conducted as part of the EU-funded project HAPPY AUDIT. A total of 2,698 patients with LRTI were included. In Denmark, 47% of the patients with LRTI were classified with a diagnosis of ...
Objectives: To obtain detailed information on current prescribing rates of antibiotics for respir... more Objectives: To obtain detailed information on current prescribing rates of antibiotics for respiratory tract infections (RTIs) in Dutch general practice and its relation with age and respiratory tract clinical entities. Methods: We assessed the mean proportion of antibiotics prescribed for RTIs per age group, contactbased and population-based using all patient contacts concerning RTIs in the year 2000 selected from the IPCI database, containing information on general practice consultations of 235 290 patients. Results: In one-third of all contacts concerning RTIs, antibiotics were prescribed, with much variation between age groups and clinical entities. For children (0-15 years) and the elderly (over 75 years), the lowest contact-based percentages of prescribed antibiotics for RTIs were found, while populationbased, children of age 0-5 years received far more antibiotics for RTIs. High prescribing rates were seen in patients with sinusitis-like complaints (67%) or pneumonia (78%), whereas low rates were found for patients with upper RTIs (16%). Conclusions: Potential over-prescribing of antibiotics for RTIs occurs in the age group 31-65 years, not in children and the elderly, and in patients with upper RTIs, sinusitis and most likely acute bronchitis (contact-based). The management of these subgroups of patients should be addressed in quality assurance programmes. Children and the elderly visit the GP much more often than adults, which can be explained by more frequent (children) or more severe (elderly) RTI morbidity, but in proportion they do not receive more antibiotics.
Background: Excessive use of antibiotics is worldwide the most important reason for development o... more Background: Excessive use of antibiotics is worldwide the most important reason for development of antimicrobial resistance. As antibiotic resistance may spread across borders, high prevalence countries may serve as a source of bacterial resistance for countries with a low prevalence. Therefore, bacterial resistance is an important issue with a potential serious impact on all countries. Initiatives have been taken to improve the quality of antibiotic prescribing in primary care, but only few studies have been designed to determine the effectiveness of multifaceted strategies across countries with different practice setting. The aim of this study was to evaluate the impact of a multifaceted intervention targeting general practitioners (GPs) and patients in six countries with different health organization and different prevalence of antibiotic resistance. Methods: GPs from two Nordic countries, two Baltic Countries and two Hispano-American countries registered patients with respiratory tract infections (RTIs) in 2008 and 2009. After first registration they received individual prescriber feedback and they were offered an intervention programme that included training courses, clinical guidelines, posters for waiting rooms, patient brochures and access to point of care tests (Strep A and C-Reactive Protein). Antibiotic prescribing rates were compared before and after the intervention. Results: A total of 440 GPs registered 47011 consultations; 24436 before the intervention (2008) and 22575 after the intervention (2009). After the intervention, the GPs significantly reduced the percentage of consultations resulting in an antibiotic prescription. In patients with lower RTI the GPs in Lithuania reduced the prescribing rate by 42%, in Russia by 25%, in Spain by 25%, and in Argentina by 9%. In patients with upper RTIs, the corresponding reductions in the antibiotic prescribing rates were in Lithania 20%, in Russia 15%, in Spain 9%, and in Argentina 5%. Conclusion: A multifaceted intervention programme targeting GPs and patients and focusing on improving diagnostic procedures in patients with RTIs may lead to a marked reduction in antibiotic prescribing. The pragmatic before-after design used may suffer from some limitations and the reduction in antibiotic prescribing could be influenced by factors not related to the intervention.
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Papers by Gloria Cordoba