Primary care Response to antibiotics of women with symptoms of urinary tract infection but negative dipstick urine test results: double blind randomised controlled trial

Objective To assess the effectiveness of antibiotic treatment of women with symptoms of urinary tract infection but negative urine dipstick testing. Design Prospective, double blind, randomised, placebo controlled trial. Setting Primary care, among a randomly selected group of general practitioners in Christchurch, New Zealand. Participants 59 women aged 16-50 years presenting with a history of dysuria and frequency in whom a dipstick test of midstream urine was negative for both nitrites and leucocytes. Participants with complicated urinary tract infection were excluded. Intervention Trimethoprim 300 mg daily for three days or placebo. Main outcome measures Self reported diary of symptoms for seven days, recording the presence or absence of individual symptoms each day, followed by a structured telephone questionnaire after seven days. The main clinical outcome was resolution of dysuria at three and seven days and median time to resolution. Secondary outcomes were resolution of other symptoms. Results The median time for resolution of dysuria was three days for trimethoprim compared with five days for placebo (P = 0.002). At day 3, five (24%) of patients in the treatment group had ongoing dysuria compared with 20 (74%) in the placebo group (P = 0.005). This difference persisted until day 7: two patients (10%) in the treatment group v 11 (41%) in the placebo group; P = 0.02). The number needed to treat was 4. The median duration of constitutional symptoms (feverishness, shivers) was reduced by four days. Conclusions Although a negative dipstick test for leucocytes and nitrites accurately predicted absence of infection when standard microbiological definitions were used (negative predictive value 92%), it did not predict response to antibiotic treatment. Three days’ treatment with trimethoprim significantly reduced dysuria in women whose urine dipstick test was negative. These results support the practice of empirical antibiotic use guided by symptoms. Balancing the competing interests of symptom relief and the minimisation of antibiotic use remains a dilemma—further research is needed to determine clinical predictors of response to antibiotics. Introduction Infections of the urinary tract are extremely common, and the numbers of patients presenting to general practice with this condition represent considerable morbidity and workload. Because the symptoms of dysuria and frequency are unpleasant, doctors are under pressure from patients to provide relief. 3 However, not all such symptoms are associated with growth of bacteria in a standard midstream urine specimen. More detailed microbiological investigation of women with apparently negative urine cultures on standard testing indicate that a proportion of them have low count bacteriuria. Urine testing with dipsticks that detect the presence of leucocytes and nitrites is commonly used in primary care to predict the subsequent diagnosis of urinary tract infection as determined by standard midstream urine culture and to guide the use of antibiotics. In one general practice study, the presence of leucocytes or nitrites in turbid urine had a positive predictive value of finding a pure growth on subsequent culture of around 66%. Conversely, a negative dipstick test for both leucocytes and nitrites has a negative predictive value of finding a pure growth on subsequent culture of 80-98.5%. 3 In 2000 we carried out an epidemiological study to determine the prevalence of antibiotic resistance in bacteria causing uncomplicated urinary tract infections in the community and confirm the negative predictive value of the dipstick. Of 374 specimens collected, 96 (26%) were negative for both leucocytes and nitrites. Eight of these (8%) contained pure growth cultures above the standard conservative cut-off point of 100×10 colony forming units per litre. The negative predictive value of the dipstick test was 92%. The approach to women with symptoms of uncomplicated urinary tract infection and positive urine dipstick results is to give empirical antibiotic treatment. Recommendations for the treatment of women with symptoms and negative dipstick results vary. Some suggest empirical treatment, 10 but others do not. 8 11 We carried out a pragmatic trial of antibiotic compared with placebo in women with symptoms of uncomplicated urinary tract infection and negative dipstick results.