Main findings
This observational study including women with suspected uUTI in primary care showed bacterial growth in 80% of urine samples. Resistance levels in E.coli were low, except for trimethoprim. The resistance levels for ciprofloxacin in E.coli were significantly lower than in routine laboratory data. Almost 74% of the women were treated with antibiotics of which the majority were primary choice antibiotics according to clinical guidelines.
Strengths and weaknesses
This is one of few studies describing bacterial findings in patients with suspected uUTI in primary care. The study design was aimed to be as similar to routine clinical practice as possible. Patients, instead of GPs, were asked to register prescribed antibiotics in the questionnaire, in order to interfere with the GPs’ prescribing as little as possible. In daily clinical practice, urine cultures from adult female patients with UTI symptoms are not analyzed and subsequently there is little knowledge about the prevalence of antimicrobial resistance among women with uUTI in primary health care. A strength of our study is that all urine cultures were analyzed at the same laboratory and that we were able to collect routine data (representing both PHC and hospital care since the laboratory does not separate primary care cultures from hospital care cultures when reporting data on resistance) on resistance in E.coli for the same time-period and the same agegroups from that laboratory. We had a high response rate regarding the questionnaires and a low internal drop out. This means that the non -response bias is low and our results are representative for the population included in this study.
It is a weakness of our study that we did not recruit the stipulated 400 patients. Since uUTIs often are managed fast in practice, we believe that patients and GPs did not take the extra time needed to fill out the questionnaire and to inform patients about the study. The total number of patients diagnosed with uUTI at included PHCCs during the study period is not known and thus the number of patients that declined to participate cannot be presented. Bladder incubation time was shorter than the recommended four hours [7]. Due to UTI-symptoms, patients often have difficulties to keep the urine in the bladder for the requested four hours. Antibiotic prescriptions followed recommendations to a high extent. It is possible that GPs, who were aware that their patients were participating in a study, prescribed antibiotics more prudently and were following guidelines to a higher extent. This issue has been described in former studies where GPs who actively chose to take part in a medical audit or who were participating in research networks prescribed fewer antibiotics than the total population of GPs [14, 15].
Previous studies
In this current study, bacterial growth was found in 80% of urine samples and growth of E.coli was identified in 72% of positive cultures. This is inline with other studies that report that E.coli causes the majority of infections among outpatients regardless of age group [16, 17]. In a previous study from out-patients in Sweden, E.coli was found in 77% of positive urine cultures from women [9].
The proportions of resistant E.coli isolates in our study were compared to the proportion of resistant E.coli isolates from the regional laboratory of microbiology during the same time period. Our data, representing women with suspected uUTI attending PHCCs, shows lower prevalence of resistance in E.coli to ciprofloxacin, which could be expected given that information on antibiotic resistance is often based on selected laboratory data with more severely ill patients. Thus in order to correctly describe antibiotic resistance in E.coli from PHC we need laboratories to be able to separate information about antibiotic resistance in isolates from PHC from isolates from hospital care.
Compared to three previous primary health care studies from different European countries our data on antibiotic resistance in E.coli shows lower resistance rates to ciprofloxacin but similar rates to trimethoprim, nitrofurantoin and cefadroxil [4, 5, 18]. In a PHC study in our neighboring country Denmark resistance rates to trimethoprim and ciprofloxacin in E.coli have been reported to 23 and 8% [19]. Also ESBL producing E.coli was more common in uUTI in Denmark as compared to Sweden [19]. Previous studies have shown large variations in antibiotic prescribing for uUTI in various countries and this may be one reason among several behind the difference in antibiotic resistance between countries [18].
Our results show that treatment with UTI-antibiotics within the last 12 months was associated with antibiotic resistance in E.coli (p < 0.001), which is in line with previous UTI studies where antibiotic resistance is associated with previous antibiotic treatment, i.e. with the strongest effect shown in the month directly after prescription but detectable up to 12 months [20]. Antibiotic consumption within the previous four weeks did not significantly affect the prevalence of resistant E.coli in our analysis and since it could interact with the variable antibiotic consumption during the last year, we excluded it in the regression analysis. By contrast to other studies, we could not find that the number of prescriptions of UTI antibiotics within the last year increased the odds for resistant E.coli [5, 21, 22]. This may be due to a rather small group of resistant E.coli in our material, other antibiotic choices and shorter duration of treatment than in previous studies. Only a few patients with growth of E.coli (n = 25) reported being treated with antibiotics within the last four weeks, due to the low number the result has to be interpreted with caution. Travelling abroad has in previous studies showed associations with ESBL in UTI [6]. In our study, travelling abroad within the last six months was associated with resistant E.coli (adjusted OR 4.02%CI 1.35–11.95).
In 2007 recommendations for the treatment of uUTI in women were published. Pivmecillinam and nitrofurantoin are recommended as first choice antibiotics, the use of cephalosporins or fluoroquinolones is no longer recommended in Sweden when treating uUTI [7]. In a Swedish PHC study on uUTI performed in 2008, one year after the publication of the recommendations, 59% of women were treated with antibiotics, trimethoprim was prescribed to 17% and fluoroquinolones to 6% [2]. This is in contrast to the present study where 74% of the women were treated with antibiotics. Trimethoprim and fluoroquinolones were prescribed to 2% of women respectively, in line with treatment recommendations. The difference in prescribing between the two studies reflects that one year is not enough to alter the prescribing pattern; it takes time before new guidelines are implemented in clinical practice.
The proportion of patients prescribed UTI antibiotics differs markedly between different European countries and range between 56 and 99% in previous European studies [23]. The wide range of antibiotic prescribing is probably due to uncertainty in diagnostic testing [23] but also likely due to differences in healthcare organization, accessibility to GPs and adherence to treatment recommendations. Previous studies suggest that strategies such as a follow up consultation or delayed prescriptions of antibiotics could decrease the high rate of antibiotic prescriptions in uUTI in primary care [24, 25]. The uncertainty in diagnostic testing may lead to both under- and overprescribing of antibiotics. In the present study 14% of patients with growth of bacteria in urine samples were not prescribed antibiotics and 49% of patients with no significant growth in urine samples were treated with antibiotics. Previous studies suggest that empirical treatment may result in up to 40–60% of women with UTI symptoms receiving antibiotics in spite of negative culture [26, 27]. It is required that better diagnostic tools are developed to target antibiotic prescription and that selected patients are offered delayed prescriptions in order to avoid unnecessary prescribing and reduce antibiotic use.
Relevance
In 2007, Swedish guidelines for the treatment of uUTI in women were published. As a result of increasing resistance levels to trimethoprim and ciprofloxacin in E.coli, pivmecillinam and nitrofurantoin were recommended as first choice antibiotics when treating uUTI [7]. Based on the results on resistance levels from the present study, pivmecillinam and nitrofurantoin are good first choice forms of treatment. The included, patients were prescribed antibiotics according to guidelines. Even though the use of pivmecillinam and nitrofurantoin was high, resistance levels were low and we found no E.coli strain resistant to nitrofurantoin.
The study also shows that resistance rates to trimethoprim are high in PHC, accordingly trimethoprim should only be used after urine culture. Further, resistance rates to ciprofloxacin were lower among patients included in this study compared with data from the clinical microbiology laboratory. The use of fluoroquinolones (ciprofloxacin) should still be avoided in the treatment of uUTI since the use of fluoroquinolones has been associated with the rise in prevalence of multi resistant bacteria. Prescribing should be limited to complicated cases and preferably after culture results.