Eva Hummers-Pradier

The Diagnosis of Urinary Tract Infection

BACKGROUND Urinary tract infections (UTI) are among the leading reasons for treatment in adult primary care medicine, accounting for a considerable percentage of antibiotic prescriptions. Because this problem is so common and so significant in routine clinical practice, a high level of diagnostic accuracy is essential. Antibiotics should not be prescribed excessively, particularly in view of the increasing prevalence of antibiotic resistance. METHOD Systematic review of relevant articles that were retrieved by a search of the Medline, Embase, and Cochrane Library databases. The recommendations of selected international guidelines were also taken into account, as were the German national quality standards for microbiological diagnosis. RESULTS The diagnosis of UTI by clinical criteria alone has an error rate of approximately 33%. The use of refined diagnostic algorithms does not completely eliminate uncertainty. CONCLUSION With the aid of a small number of additional diagnostic criteria, antibiotic treatment for UTI can be provided more specifically and thus more effectively. Differentiating UTI from asymptomatic bacteriuria, which usually requires no treatment, can lower the frequency of unnecessary antibiotic prescriptions.

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

Determination of bleeding risk using genetic markers in patients taking phenprocoumon

BackgroundIn patients on oral anticoagulation with warfarin, genetic variations of the cytochrome P 450–CYP2C9 have recently been associated with very low warfarin requirements. Patients needing low doses had an increased risk for bleeding complications. In Germany, phenprocoumon (having a similar metabolic pathway) is the most commonly employed vitamin K antagonist. Treatment is usually monitored by general practitioners (GPs).ObjectivesTo determine whether CYP2C9 variant alleles can serve as risk markers in general-practice patients anticoagulated with phenprocoumon.MethodsAll adult anticoagulated patients in 12 teaching general practices and one university outpatient clinic were to be recruited. Blood samples were taken from 185 patients during routine anticoagulation controls and tested for CYP2C9 mutations. Subjects answered a questionnaire concerning bleeding complications, drug intolerance, and personal and family medical history. Phenprocoumon dosages required for stable anticoagulation were recorded. Odds ratios (OR) with 95% confidence intervals (CI) were calculated based on 2-way cross-tabulations and multivariate logistic regression models, t-tests used where appropriate.ResultsBleeding was reported by 19% of the patients, 2.2% of whom had suffered life-threatening bleeding. CYP2C9 variants were carried by 26.3% of 179 patients tested (17.9% *1/*2, 7.8% *1/*3, 0.6% *2/*3). While presence of a *2 allele was not associated with an increased risk (OR 0.35, CI 0.10–1.24), carriers of the rare *3 alleles had a higher risk of bleeding (OR 3.10, CI 1.02–9.40). With regard to bleeding, carrying CYP2C9*3 was highly specific (94%), though sensitivity was low at 17%; post-test probability of bleeding was 40%.ConclusionsCYP2C9*3 variants are associated with an increased bleeding risk in patients anticoagulated with phenprocoumon. Screening can identify patients with a high risk of bleeding. Appropriate clinical consequences (restricted indication for anticoagulation, careful induction, adjustment of target INR, closer monitoring or self-testing of INR) as well as the cost-effectiveness of screening for variant CYP2C9 with regard to patient outcomes should be subject of further research.

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.

Urinary tract infection in men

OBJECTIVE To explore the prevalence and microbiology of urinary tract infection (UTI) in symptomatic men in a primary care setting and to determine the appropriateness of patient management of these conditions by the general practitioners. METHODS A cross-sectional survey was carried out matching documentation of symptoms and management with urine culture and results of susceptibility tests. All patients presenting with symptoms typical for a UTI in 36 teaching general practices in the area of Göttingen, Germany, were eligible for enrolment in the study. 15% (n = 90) of all patients were adult men. General practitioners (GPs) were instructed to manage patients as usual. Patient characteristics, dipstick tests and treatment were matched with results of urine cultures and susceptibility testing. RESULTS Men presenting with symptoms indicative of UTI were predominantly elderly (median age 61 years) and 41% had additional risk factors. Antibiotics were prescribed for 36%, but these were not well-targeted. Urine culture revealed UTI in 60%, of which half had low colony counts (23% of all patients) or multiple bacterial growth (7%); 40% had sterile urine. Dipstick tests proved unhelpful: leukocytes and nitrite had sensitivities of 54% and 38%, specificities of 55% and 84%, positive predictive values of 65% and 78% and negative predictive values of 44% and 46%, respectively. Resistance levels were 53% for amoxicillin and cefaclor, 28% for cefixim, 22% for ciprofloxacin, 34% for both trimethoprim as individual substance and the combination with sulfamethoxazole (cotrimoxazole) and 25% for nitrofurantoin. CONCLUSION Men with symptoms indicative of a UTI should not be treated empirically. A urine culture and antibiogram should be obtained before a treatment decision is made. A low-count UTI was common and should not be considered normal.

Drug changes at the interface between primary and secondary care

OBJECTIVE To analyze the frequency and factors associated with drug change in a sample of patients referred to hospital by their general practitioner. METHODS This observational study is based on a chart review of 100 consecutively recruited patients with a chronic disease who were referred to the general internal medicine wards in each of 3 district general hospitals in Germany (total 300 patients). The frequency of drug cancellation, replacement, dosage alteration, change in manufacturer and of commencing treatment with a new drug were recorded. RESULTS Half of the drugs used in chronic treatment (644/1,330) and prescribed by general practitioners were continued during hospitalization. The fraction canceled was 36%. In the rest of the drugs in this group, there were some minor changes carried out by the hospital. On the day of the drug survey, a total of 1,572 drugs were being taken by the patients and 724 of these drugs were newly prescribed by hospital. Only 13 patients experienced no change to their drug regimen during their stay in hospital. In more than 60% of patients (184/300), there were 3 or more changes made in their drug regimen. The rate of drug cancellation for antihypertensive and cardiac drugs in patients referred to hospital for cardiovascular and non-cardiovascular problems did not differ. CONCLUSION During hospitalization, nearly every patient is confronted with some form of drug change. Of major concern is the high rate of drug change affecting drugs being taken for diseases other than that associated with the hospitalization. Hospital drug policy should encourage clinicians to continue drug regimens in newly admitted patients whenever medically appropriate and caution clinicians against making unnecessary changes to drug regimens prescribed by general practitioners.

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.

The research agenda for general practice/family medicine and primary health care in Europe. Part 3. Results: Person centred care, comprehensive and holistic approach

Abstract The recently published ‘Research Agenda for General Practice/Family Medicine and Primary Health Care in Europe’ summarizes the evidence relating to the core competencies and characteristics of the Wonca Europe definition of GP/FM, and its implications for general practitioners/family doctors, researchers and policy makers. The European Journal of General Practice publishes a series of articles based on this document. In a first article, background, objectives, and methodology were discussed. In a second article, the results for the two core competencies ‘primary care management’ and ‘community orientation’ were presented. This article reflects on the three core competencies, which deal with person related aspects of GP/FM, i.e. ‘person centred care’, ‘comprehensive approach’ and ‘holistic approach’. Though there is an important body of opinion papers and (non-systematic) reviews, all person related aspects remain poorly defined and researched. Validated instruments to measure these competencies are lacking. Concerning patient-centredness, most research examined patient and doctor preferences and experiences. Studies on comprehensiveness mostly focus on prevention/care of specific diseases. For all domains, there has been limited research conducted on its implications or outcomes.

Antibiotic resistance of urinary pathogens in female general practice patients

A cross-sectional study was performed to determine the prevalence of antibiotic resistance in women with uncomplicated and complicated lower urinary tract infection (UTI) in Germany. In 36 (of 118 invited) general practices, urine cultures and resistance testing were performed during 4 months on all women presenting with symptoms of UTI. Each patients symptoms, risk factors and treatment were documented. A total of 445 women were included, and their median age was 53 y. Complicating factors were present in 27% of women. Urine cultures were available for 430 patients. They were sterile in 23%, 53% had 105 cfu/ml or more, and 24% had 102–104 cfu/ml. E.coli was the most frequent pathogen (68%), followed by Enterococcus faecalis (10%) and Proteus spp. (10%). E.coli resistance levels were 25–40% for amoxicillin, co-amoxiclav, first generation oral cephalosporins, trimethoprim and co-trimoxazole. Nine percent were resistant to fluoroquinolones. E.coli resistance remained low for nitrofurantoin (2%) and third generation oral cephalosporins (3%). Odds for E.coli resistance to most antibiotics were 2–5 times higher in patients with complicating factors, and increased with age. Resistance levels to all common antibiotics were high even in unselected females with UTI in general practices. Older or complicated patients had a significantly higher risk for resistance.

Job Satisfaction Among Primary Care Physicians: Results of a Survey

BACKGROUND A shortage of primary care physicians (PCPs) seems likely in Germany in the near future and already exists in some parts of the country. Many currently practicing PCPs will soon reach retirement age, and recruiting young physicians for family practice is difficult. The attractiveness of primary care for young physicians depends on the job satisfaction of currently practicing PCPs. We studied job satisfaction among PCPs in Lower Saxony, a large federal state in Germany. METHODS In 2009, we sent a standardized written questionnaire on overall job satisfaction and on particular aspects of medical practice to 3296 randomly chosen PCPs and internists in family practice in Lower Saxony (50% of the entire target population). RESULTS 1106 physicians (34%) responded; their mean age was 52, and 69% were men. 64% said they were satisfied or very satisfied with their job overall. There were particularly high rates of satisfaction with patient contact (91%) and working atmosphere (87% satisfied or very satisfied). In contrast, there were high rates of dissatisfaction with administrative tasks (75% dissatisfied or not at all satisfied). The results were more indifferent concerning payment and work life balance. Overall, younger PCPs and physicians just entering practice were more satisfied than their older colleagues who had been in practice longer. CONCLUSION PCPs are satisfied with their job overall. However, there is significant dissatisfaction with administrative tasks. Improvements in this area may contribute to making primary care more attractive to young physicians.