12 March 2010
A randomised controlled trial found that there was no advantage in routinely treating simple UTIs on the basis of urine bacteriology results. Using delayed antibiotics or targeting antibiotics by dipstick results with delayed antibiotics as back up, were both effective in controlling symptoms overall compared to immediate antibiotics, and reduced antibiotic use. An economic study of the strategies, a qualitative study of women’s attitudes and an observational study added more information.
Level of evidence:
Main study: Level 1 (good quality patient-oriented evidence) according to the SORT criteria.
In accordance with advice from the Health Protection Agency, routine urine culture (midstream urine, MSU) is unnecessary in simple lower urinary tract infection. If a bacterial infection is likely (no vaginal discharge plus three or more of dysuria, urgency, frequency, polyuria, suprapubic tenderness or haematuria) then a strategy of immediate or delayed antibiotics (depending on patient preference) seems reasonable. A 3 day course of trimethoprim or nitrofurantoin is the regimen of choice here.
If the diagnosis is in doubt, using dipsticks to guide treatment (including an option of back-up delayed antibiotics) is probably appropriate. It is important that women are offered explanation and reassurance, especially if a delayed antibiotic strategy is offered. Pyelonephritis, UTIs in men, the elderly, children, or pregnant women, or those that recur, require different management from simple lower UTIs.
What is the background to this?
The issues around management of urinary tract infection (UTI) are discussed in a linked editorial. UTI is one of the most common conditions seen in women in primary care, affecting half of all women at least once in their lives. UTI symptoms are unpleasant and antibiotics are often prescribed empirically, but many women with confirmed bacteriological UTI will recover without them. In addition, a substantial proportion of women with clinically identical symptoms of UTI do not have detectable bacteriological infection but do have a symptomatic response to empirical antibiotics The problem with empirical treatment is that 10% of the healthy adult female population would receive antibiotics each year. The use of antibiotics to this extent in the population has implications for antibiotic resistance.
These studies attempted to consider the alternatives to empirical antibiotics in simple lower UTI in terms of clinical effectiveness, cost effectiveness, and acceptability to women; and to study the epidemiology of UTIs
In the first, a randomised controlled trial (RCT), 309 women with suspected uncomplicated UTI were randomised to five management approaches:
- empirical antibiotics (trimethoprim 200mg twice daily for 3 days, or cefaclor or cefalexin in those allergic to trimethoprim)
- a delayed prescription for antibiotics (ie start antibiotics if no improvement after 48 hours)
- targeted antibiotics based on a symptom score (empirical antibiotic if two or more of urine cloudiness, offensive urine smell, nocturia, or dysuria). Patients without 2 or more features were offered a delayed antibiotic prescription to use if their symptoms were not settling after 48 hours
- targeted antibiotics based on a dipstick result (empirical antibiotic if positive for nitrites, or leucocytes and a trace of blood). Other patients were offered a delayed antibiotic prescription to use if their symptoms were not settling after 48 hours
- MSU taken, symptomatic treatment until results obtained, then targeted antibiotics if a positive result.
Self help advice was controlled in each group.
Linked researchers also conducted a qualitative study in 21 of these women to explore their views on the acceptability of the different strategies for managing the infection and the cause of infection. A further study assessed the cost effectiveness of the different management strategies. Finally and an observational study in 839 women assessed the natural course and the important predictors of severe symptoms in UTI and the effect of antibiotics and antibiotic resistance.
What does this study claim?
In the RCT, the average duration of symptoms rated as moderately bad or worse with immediate antibiotics was 3.5 days. Overall, there were no significant differences in symptom duration, severity of frequency symptoms (increased day frequency, increased night frequency, and urgency and dysuria), or severity of ‘unwell’ symptoms (abdominal pain, restricted activities, and feeling unwell) between the antibiotic management strategies. The confidence intervals for symptom severity suggest that differences between the dipstick, symptom score, and delayed antibiotics groups are unlikely to be clinically important.
Women who waited for at least 48 hours before using their prescription reconsulted less (hazard ratio 0.57, 95%CI 0.36 to 0.89, P=0.014). However, these women were likely to have 37% longer duration of symptoms rated as moderately bad (incidence rate ratio 1.37 (95%CI 1.11 to 1.68), P<0.001). The effect of delaying more than 48 hours predominantly applied to the MSU group (P=0.02). Women in the delayed antibiotic, dipstick and MSU groups were less likely to use antibiotics than those in the symptom score and immediate antibiotic groups (delayed antibiotics 77%, dipstick 80%, MSU 81%, symptom score 90%, immediate antibiotics 97%, P=0.011).
Cost effectiveness analysis suggested that if avoiding a day of moderately bad symptoms was valued at less than £10, then immediate antibiotics is likely to be the most cost effective strategy. If this outcome is valued at greater than £10, targeted antibiotics with dipstick testing becomes the most cost effective strategy, although because of the uncertainty we can never be more than 70% certain that this strategy truly is the most cost effective.
In the observational study, outcomes were compared in different situations compared with those for women with sensitive infections given antibiotics. After adjustment for other predictors, moderately bad symptoms lasted 56% longer (incidence rate ratio 1.56, 95%CI 1.22 to 1.99, P<0.001) in women with resistant infections; 62% longer (1.62, 95%CI 1.13 to 2.31, P=0.008) when no antibiotics were prescribed; and 33% longer (1.33, 95%CI 1.14 to 1.56, P<0.001) in women with urethral syndrome. The duration of symptoms was shorter if the doctor was perceived to be positive about diagnosis and prognosis (continuous 7 point scale: 0.91, 95%CI 0.84 to 0.99; P=0.021) and longer when the woman had frequent somatic symptoms (1.03, 95%CI 1.01 to 1.05, P=0.002; for each symptom), a history of cystitis, urinary frequency, and more severe symptoms at baseline.
Finally, the qualitative study found that women generally preferred not to take antibiotics and were open to alternative management approaches. With a strategy of ‘antibiotic delay’ some women felt a lack of validation or that they were not listened to by their GP. Women attributed UTI to lifestyle habits and behaviours, such as poor hygiene, general ‘negligence,’ and even a ‘penalty of growing old.’
These studies are all based on five common approaches to managing simple UTI. It is clear that delaying treatment until the result of an MSU sample is available is undesirable, from both a clinical and cost-effectiveness perspective.
The HPA states that women with the combination of no vaginal discharge plus three or more of dysuria, urgency, frequency, polyuria, suprapubic tenderness or haematuria have a 90% likelihood of bacterial infection (high positive predictive value). In women with this presentation, the options are immediate antibiotics, delayed antibiotics to be commenced if symptoms do not show signs of improvement after 48 hour, or even no antibiotics (given that many women with confirmed bacteriological UTI will recover without antibiotics, and they may wish to avoid the risk of side effects). A patient decision aid is available from the NPC which may be helpful in discussions with patients.
The choice between immediate and delayed antibiotics involves a trade-off between reducing unnecessary antibiotic use (and so reducing the risk of side effects such as thrush and the risk of encouraging resistance, which could have personal and public health implications) and increasing the risk of longer duration of more unpleasant symptoms.
If the urine is not cloudy and symptoms are mild or there are only one or two of dysuria, urgency, frequency, polyuria, suprapubic tenderness or haematuria, the chance of a bacterial infection is only around 9% (high negative predictive value). In women with this presentation, no antibiotics or a delayed antibiotic strategy seems appropriate.
Using dipstick tests to help identify the women with a bacterial infection may be helpful, but given the clinically important risk of false negatives, it would be best to limit their use to situations when the diagnosis is not straightforward, else a dipstick result might be misleading. Such situations include mild symptoms or only one or two of dysuria, urgency, frequency, polyuria, suprapubic tenderness or haematuria; but with cloudy urine.
Little P, et al Presentation, pattern, and natural course of severe symptoms, and role of antibiotics and antibiotic resistance among patients presenting with suspected uncomplicated urinary tract infection in primary care: observational study. BMJ 2010;340:b5633
The key results are discussed above.
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