Jutta Bleidorn

Symptomatic treatment (ibuprofen) or antibiotics (ciprofloxacin) for uncomplicated urinary tract infection? - Results of a randomized controlled pilot trial

BackgroundUncomplicated lower urinary tract infections (UTI) are usually treated with antibiotics. However, there is little evidence for alternative therapeutic options.This pilot study was set out 1) to make a rough estimate of the equivalence of ibuprofen and ciprofloxacin for uncomplicated urinary tract infection with regard to symptom resolution, and 2) to demonstrate the feasibility of a double-blind, randomized controlled drug trial in German general practices.MethodsWe performed a double-blind, randomized controlled pilot trial in 29 German general practices. Eighty otherwise healthy women aged 18 to 85 years, presenting with at least one of the main UTI symptoms dysuria and frequency and without any complicating factors, were randomly assigned to receive either ibuprofen 3 × 400 mg oral or ciprofloxacin 2 × 250 mg (+1 placebo) oral, both for three days.Intensity of main symptoms - dysuria, frequency, low abdominal pain - was recorded at inclusion and after 4, 7 and 28 days, scoring each symptom from 0 (none) to 4 (very strong). The primary endpoint was symptom resolution on Day 4. Secondary outcomes were the burden of symptoms on Days 4 and 7 (based on the sum score of all symptoms), symptom resolution on Day 7 and frequency of relapses. Equivalence margins for symptom burden on Day 4 were pre-specified as +/- 0.5 sum score points. Data analysis was done by intention to treat and per protocol. Randomization was carried out on patient level by computer programme in blocks of six.ResultsSeventy-nine patients were analyzed (ibuprofen n = 40, ciprofloxacin n = 39). On Day 4, 21/36 (58.3%) of patients in the ibuprofen-group were symptom-free versus 17/33 (51.5%) in the ciprofloxacin-group. On Day 4, ibuprofen patients reported fewer symptoms in terms of total sum score (1; SD 1,42) than ciprofloxacin patients (1,3; SD 1,9), difference -0,33 (95% CI (-1,13 to +0,47)), PP (per protocol) analysis. During Days 0 and 9, 12/36 (33%) of patients in the ibuprofen-group received secondary antibiotic treatment due to ongoing or worsening symptoms, compared to 6/33 (18%) in the ciprofloxacin-group (non significant). A total of 58 non-serious adverse events were reported, 32 in the ibuprofen group versus 26 in the ciprofloxacin group (non significant).ConclusionsOur results support the assumption of non-inferiority of ibuprofen compared to ciprofloxacin for treatment of symptomatic uncomplicated UTI, but need confirmation by further trials.Trial registrationTrial registration number: ISRCTN00470468See Commentary http://www.biomedcentral.com/1471-2296/11/42

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.

Resistance profiles of urinary tract infections in general practice - an observational study

BackgroundGuideline recommendations on therapy in urinary tract infections are based on antibiotic resistance rates. Due to a lack of surveillance data, little is known about resistance rates in uncomplicated urinary tract infection (UTI) in general practice in Germany. In a prospective observational study, urine cultures of all women presenting with urinary tract infections in general practice were analysed. Resistance rates against antibiotics recommended in German guidelines on UTI are presented.MethodsIn a prospective, multi-center observational study general practitioner included all female patients ≥ 18 years with clinically suspected urinary tract infection. Only patients receiving an antibiotic therapy within the last two weeks were excluded.Results40 practices recruited 191 female patients (mean age 52 years; range 18–96) with urinary tract infections. Main causative agent was Escherichia coli (79%) followed by Enterococcus faecalis (14%) and Klebsiella pneumoniae (7.3%).Susceptibiliy of E.coli as the main causative agent was highest against fosfomycin and nitrofurantoin, with low resistance rates of 4,5%; 2,2%. In 17,5%, E.coli was resistant to trimethoprim and in 8,5% to ciprofloxacin.ConclusionsResistance rates of uropathogens from unselected patients in general practice differ from routinely collected laboratory data. These results can have an impact on antibiotic prescribing and treatment recommendations.

Immediate versus conditional treatment of uncomplicated urinary tract infection - a randomized-controlled comparative effectiveness study in general practices

BackgroundUncomplicated urinary tract infections (UTI) are usually treated with antibiotics as recommended by primary care guidelines. Antibiotic treatment supports clinical cure in individual patients but also leads to emerging resistance rates in the population. We designed a comparative effectiveness study to investigate whether the use of antibiotics for uncomplicated UTI could be reduced by initial treatment with ibuprofen, reserving antibiotic treatment to patients who return due to ongoing or recurrent symptoms.Methods/designThis is a randomized-controlled, double-blind, double dummy multicentre trial assessing the comparative effectiveness of immediate vs. conditional antibiotic therapy in uncomplicated UTI. Women > 18 and < 65 years, presenting at general practices with at least one of the typical symptoms dysuria or frequency/urgency of micturition, will be screened and enrolled into the trial. During an 18- months recruitment period, a total of 494 patients will have to be recruited in 45 general practices in Lower Saxony. Participating patients receive either immediate antibiotic therapy with fosfomycin-trometamol 1x3g or initial symptomatic treatment with ibuprofen 3x400mg for 3 days. The ibuprofen group will be provided with antibiotic therapy only if needed, i.e. for persistent or worsening symptoms. For a combined primary endpoint, we choose the number of all antibiotic prescriptions regardless of the medical indication day 0–28 and the “disease burden”, defined as a weighted sum of the daily total symptom scores from day 0 to day 7. The study is considered positive if superiority of conditional antibiotic treatment with respect to the first primary endpoint and non-inferiority of conditional antibiotic treatment with respect to the second primary endpoint is proven.DiscussionThis study aims at investigating whether the use of antibiotics for uncomplicated UTI could be reduced by initial treatment with ibuprofen. The comparative effectiveness design was chosen to prove the effectiveness of two therapeutic strategies instead of the pure drug efficacy.Trial registrationClinicaltrials.Gov: NCT01488955

General practice-based clinical trials in Germany - a problem analysis

BackgroundIn Germany, clinical trials and comparative effectiveness studies in primary care are still very rare, while their usefulness has been recognised in many other countries. A network of researchers from German academic general practice has explored the reasons for this discrepancy.MethodsBased on a comprehensive literature review and expert group discussions, problem analyses as well as structural and procedural prerequisites for a better implementation of clinical trials in German primary care are presented.ResultsIn Germany, basic biomedical science and technology is more reputed than clinical or health services research. Clinical trials are funded by industry or a single national programme, which is highly competitive, specialist-dominated, exclusive of pilot studies, and usually favours innovation rather than comparative effectiveness studies. Academic general practice is still not fully implemented, and existing departments are small. Most general practitioners (GPs) work in a market-based, competitive setting of small private practices, with a high case load. They have no protected time or funding for research, and mostly no research training or experience. Good Clinical Practice (GCP) training is compulsory for participation in clinical trials. The group defined three work packages to be addressed regarding clinical trials in German general practice: (1) problem analysis, and definition of (2) structural prerequisites and (3) procedural prerequisites. Structural prerequisites comprise specific support facilities for general practice-based research networks that could provide practices with a point of contact. Procedural prerequisites consist, for example, of a summary of specific relevant key measures, for example on a web platform. The platform should contain standard operating procedures (SOPs), templates, checklists and other supporting materials for researchers.ConclusionAll in all, our problem analyses revealed that a substantial number of barriers contribute to the low implementation of clinical research in German general practice. Some issues are deeply rooted in Germany’s market-based healthcare and academic systems and traditions. However, new developments may facilitate change: recent developments in the German research landscape are encouraging.

Complex health care decisions with older patients in general practice: Patient-centeredness and prioritization in consultations following a geriatric assessment

OBJECTIVE To examine to what extent general practitioners in consultations after a geriatric assessment set shared health priorities with older patients experiencing multimorbidity and to what extent this was facilitated through patient-centered behavior. METHODS Observation of consultations embedded in a cluster randomized controlled trial,(1) in which 317 patients from 41 general practices received the STEP assessment followed by a care planning consultation with their GPs. GPs in the intervention group used a structured procedure for setting health (care) priorities in contrast to control GPs. A sample of 43 consultations (24 intervention; 19 control) were recorded, transcribed and analyzed with regard to priority setting and patient-centeredness. RESULTS Patient-centeredness was only moderately apparent in consultations dealing with complex care plans for older patients with multimorbidity. The shared determination of health priorities seemed unusual for both doctors and patients and was rarely practiced, albeit more frequently in intervention consultations. CONCLUSION Setting health care priorities with patients experiencing multimorbidity is ethically desirable and medically appropriate. Yet a short structured guide for doctors cannot easily achieve this. PRACTICE IMPLICATIONS More research is needed in regard to handling complex health needs of older patients. It requires a professional approach and training in patient-centered holistic care planning.

End of life care for frail older patients in family practice (ELFOP) – protocol of a longitudinal qualitative study on needs, appropriateness and utilisation of services

BackgroundFrail elderly people represent a major patient group in family practice. Little is known about the patients’ needs, and how their needs evolve over time with increasing frailty towards the end of life. This study will address end-of-life care needs, service utilisation, and experiences of frail elderly patients and their informal caregivers, with regard to family practice. This paper aims to introduce the research protocol.Methods/DesignThe study uses a multiple perspective approach qualitative design. The first study part consists of serial six-monthly in-depth interviews with 30 community-dwelling elderly patients (≥70 years) with moderate to severe frailty and their key informal caregivers, over a period of 18 months. Additionally, semi-structured interviews with the patients’ family physician will be conducted. The serial interviews will be analysed with grounded theory and narrative approaches. Special attention will be paid to the comparison of distinct views of the patients’, informal caregivers’, and family physicians’ as well as on chronological aspects. In the second study part, five focus groups with experts in family medicine, geriatrics, palliative medicine, and nursing will be conducted. Finally, the implications for family practice and health care policy will be discussed in an expert workshop.DiscussionTo our knowledge, this is the first prospective, longitudinal qualitative study on the needs of elderly patients with advanced frailty towards the end of life in German family practice, which integrates the perspectives of patients, informal caregivers, family physicians and other health professionals. The study will contribute to the understanding of the clinical, psychosocial and information needs of patients and their caregivers, and of respective changes of experiences and needs along the illness/frailty trajectory including the last phase of life. It will provide an empirical basis for improving patient-centred care for this increasingly relevant target group.

Recurrent urinary tract infections and complications after symptomatic versus antibiotic treatment: follow-up of a randomised controlled trial.

Background: Uncomplicated urinary tract infections (UTI) are common in general practice, and are usually treated with antibiotics. Recurrent UTI often pose a serious problem for affected women. Little is known about recurrent UTI and complications when uncomplicated UTI are treated without antibiotics. With ICUTI (Immediate vs. conditional antibiotic use in uncomplicated UTI, funded by BMBF No. 01KG1105) we assessed whether initial symptomatic treatment with ibuprofen could be a treatment alternative for uncomplicated UTI. The presented analysis aims to assess the influence of initial (non-)antibiotic treatment on recurrent UTI rates and pyelonephritis after day 28 up to 6 months after trial participation. Methods: This study is a retrospective long-term follow-up analysis of ICUTI patients, surveyed telephonically six months after inclusion in the trial. Recurrent UTI, pyelonephritis or hospitalizations were documented. Statistical evaluation was performed by descriptive and multivariate analyses with SPSS 21. Results: For the six months follow-up survey, 386 trial participants could be contacted (494 had been included in ICUTI initially, 446 had completed the trial). From day 28 until 6 months after inclusion in ICUTI, 84 recurrent UTI were reported by 80 patients. Univariate and multivariate analyses showed no effect of initial treatment group or antibiotic treatment on number of patients with recurrent UTI. Yet, both analyses showed that patients with a history of previous UTI had significantly more often recurrent UTI. Pyelonephritis occurred in two patients of the antibiotic group and in one patient in the non-antibiotic group. Conclusion: This follow-up analysis of a trial comparing antibiotic vs. symptomatic treatment for uncomplicated UTI showed that non-antibiotic treatment has no negative impact on recurrent UTI rates or pyelonephritis after day 28 and up to six months after initial treatment. Thus, a four week follow-up in UTI trials seems adequate.

Predicting antibiotic prescription after symptomatic treatment for urinary tract infection: development of a model using data from an RCT in general practice

Background Uncomplicated urinary tract infection (UTI) is often treated with antibiotics, resulting in increasing resistance levels. A randomised controlled trial showed that two-thirds of females with UTI treated symptomatically recovered without subsequent antibiotic treatment. Aim To investigate whether there are differences between females with a UTI who were subsequently prescribed antibiotics and those who recovered with symptomatic treatment only, and to develop a model to predict those who can safely and effectively be treated symptomatically. Design and setting This is a subgroup analysis of females assigned to ibuprofen in a UTI trial in general practices. Method Multiple logistic regression analysis was used to select variables for a prediction model, The discriminative value of the model was estimated by the area under the receiver operator curve (AUC) and the effects of different thresholds were calculated within the model predicting antibiotic prescription and need for follow-up visits. Results Of the 235 females in the ibuprofen group, 79 were subsequently prescribed antibiotics within 28 days of follow-up. The final model included five predictors: urgency/frequency, impaired daily activities, and positive dipstick test results for erythrocytes, leucocytes, and nitrite. The AUC was 0.73 (95% CI = 0.67 to 0.80). A reasonable threshold for antibiotic initiation would result in 58% of females presenting with UTI being treated with antibiotics. Of the remaining females, only 6% would return to the practice because of symptomatic treatment failure. Conclusion The present model revealed moderately good accuracy and could be the basis for a decision aid for GPs and females to find the treatment option that fits best.

Caring for frail older people in the last phase of life – the general practitioners’ view

BackgroundFrail older people are an increasingly important group in primary care due to demographic change. For these patients, a palliative care approach may be useful to sustain the quality of life in the last phase of their lives. While general practitioners (GPs) play a key role in the primary care for older patients, general palliative care is still in its infancy and little is known in Germany about caring for frail older people towards the end of life. This study aims to explore the tasks and challenges regarding the care for frail older patients in the last phase of life from the GPs’ point of view, and the latter’s perception of their own role and responsibilities.MethodsExplorative qualitative study based on semi-structured in-depth interviews with 14 GPs from urban and rural regions in Lower Saxony, Germany. Analysis was carried out according to the principles of Grounded Theory.ResultsThe GPs’ key commitment “caring for frail older patients until the end” as an integral part of primary care was worked out as a key category, flanked by central issues: “causal conditions and challenges,” which include patients’ preconditions and care needs as well as communication and cooperation aspects on the carers’ level. “Barriers and facilitators within the health system” refers to prerequisites of the German healthcare system, such as high caseloads. Regarding “strategies to comply with this commitment”, various self-developed strategies for the care of frail older people are presented, depending on the GPs’ understanding of their professional role and individual circumstances.ConclusionsThe GPs show a strong commitment to caring for the frail older patients until the end of life. However, it is a challenging and complex task that requires significant time, which can take GPs to their limits. There is a great need to improve patient—and family-centered proactive communication, as well as interprofessional cooperation. Strengthening the team approach in primary care could relieve the burden on GPs, especially in rural areas, while simultaneously improving end-of-life care for their patients.