Postgraduate Medical School, University of Surrey, Stirling House, Surrey Research Park, Guildford GU2 7DJ, UK
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Abstract |
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Introduction |
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The UK Chief Medical Officer has indicated that resistance to commonly used antibiotics is a major threat to public health. The goals set for the National Health Service (NHS) include minimizing morbidity and mortality due to antimicrobial-resistant infection, contributing to the control of antimicrobial-resistant organisms and facilitating more efficient and effective use of NHS resources.10 When considering the management of urinary tract infections (UTIs) in young women, the issues of efficiency and effectiveness probably guide general practitioner prescribing in the UK. Empirical prescribing of antibiotics is cost effective.11 The choice of antibiotic will be influenced by knowledge of the resistance patterns of urinary pathogens locally, although the correlation between in vitro resistance and clinical outcome is far from absolute.7
The aim of this study was to describe the pattern of antibiotic prescribing to young women presenting with signs of new UTI, and to investigate the proportion who will require further treatment if prescribed antibiotic. A secondary aim was to investigate whether the likelihood of treatment failure varied between different antibiotics and, in the case of trimethoprim, the antibiotic most frequently prescribed for UTIs, between prescriptions of different duration.
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Materials and methods |
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The study population included all women aged 1544 years between 1992 and 1999 with at least 6 months data on the GPRD. Patients were followed from initial registration, and all new' diagnoses of a UTI or cystitis, as indicated by the appropriate symptom code, were identified. A new' diagnosis was defined as a UTI in a patient with no record of these symptoms during the preceding 6 months. Pregnancy or diabetes at the time of the event was identified from the patient records. Data were not generally available on the results of urine analysis. The antibiotic prescribed on the date of the record of cystitis/ UTI was identified, allowing the patterns of prescribing to be described. All patients with a diagnosis plus a prescription were then followed for 28 days and any further prescriptions of an antibiotic were noted. The need for a further antibiotic during this time was taken to indicate failure of the initial treatment. All products classified as antibacterial drugs' by the BNF were included as antibiotics. Antifungals were not considered.
There is no requirement for prescribing data to be linked to a symptom code within the GPRD. To account for the possibility that the initial (or subsequent) antibiotic treatments were not given for the UTI, all antibiotic prescriptions issued between 1992 and 1999 for women aged 1544 were selected from the database. The symptom codes on the day of the prescription were identified for each patient to create a list of potential antibiotic indications. This list was then checked by hand and all likely indications for antibiotic prescribing were retained. Patients were excluded from the analysis if they had a prescription for an antibiotic at any time in the 6 months before diagnosis or a record of any other indication for antibiotic treatment on the day of the UTI or during the following 28 days.
Cox regression analyses were conducted to examine the time before treatment failure, accounting for age, year of treatment, diabetes and pregnancy. Patients who did not receive a second antibiotic were censored on the 28th day. Failure rates were compared for the 10 antibiotics most frequently prescribed for a UTI during the study period. The percentage of patients failing at 7, 14, 21 and 28 days were calculated for each antibiotic. To maintain statistical independence, only the first new infection, with an accompanying prescription for an antibiotic issued on the same day, is included for each patient. This was termed the first infection'.
Additional analyses were undertaken comparing trimethoprim prescriptions of 3, 5 and 7 days' duration to assess whether the length of prescription influenced the likelihood of treatment failure. The analysis included all first infections' of known duration treated with trimethoprim included in earlier analyses, together with the records for patients who had received another antibiotic for a first infection, but trimethoprim for a subsequent new event. As before, to be included these additional patients had to have no record of UTI/cystitis or antibiotic treatment in the 6 months before the infection treated with trimethoprim; each patient was included in the analysis only once. The prescription duration was ascertained where the number of days of treatment was recorded in the patient's records, or where the prescription quantity and daily dose were both given, allowing duration to be calculated directly.
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Results |
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The 10 antibiotics most frequently associated with a diagnosis of UTI/cystitis are shown in Table 1, with trimethoprim being prescribed most frequently (61%) followed by amoxicillin (14%) and then cefalexin (10%). Prescribing of co-trimoxazole for new UTIs declined from 8.6% in 1992 to <0.1% in 1999 (Table 2
). Prescribing of cefalexin increased from 8% to 20% of prescriptions over the same period.
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If trimethoprim is considered the reference antibiotic, after 28 days patients prescribed amoxicillin were significantly more likely to require a second course of antibiotics (HR 1.17, 95% CI 1.11, 1.24, adjusted for age, year, pregnancy and diabetes) whereas those prescribed cotrimoxazole were significantly less likely to require further treatment (HR 0.84, 95% CI 0.75, 0.95). There was no significant difference between trimethoprim and the cephalosporins, nitrofurantoin, norfloxacin or ciprofloxacin (Table 3). The results remained unchanged if the analysis was restricted to patients with no record of pregnancy or diabetes (results not shown).
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Table 4 shows the absolute risk of a treatment failure at 7, 14, 21 and 28 days for each of the 10 most commonly prescribed antibiotics. At 28 days if co-trimoxazole had been chosen rather than trimethoprim, there would be a reduction in the failure rate from 13.3% to 11.4% or an absolute risk reduction (ARR) of 1.9%. This translates to a number needed to treat (NNT) of 53, i.e. the number of patients that would need to be prescribed co-trimoxazole rather than trimethoprim before one patient would be prevented from having a second course of antibiotics, is 53 (95% CI 33, 149).13 Similarly, with amoxicillin the difference in failure rate is 2.2% or 45 (95% CI 34, 67) patients needed to be treated with trimethoprim rather than amoxicillin to prevent one extra repeat antibiotic prescription.
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Discussion |
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A recent systematic review of randomized controlled trials (RCTs) comparing 7 day treatments of cystitis with trimethoprim and co-trimoxazole suggested that there is little difference in rates of eradication of bacteriuria 7 days after the end of therapy. Suitable data were not available to allow a similar analysis of recurrence rates.16 The results here indicate that if co-trimoxazole rather than trimethoprim was used as a first-line antibiotic, then 53 patients would need to be treated to prevent one further patient returning. The clinical significance of this may be marginal. The reason for switching to trimethoprim from co-trimoxazole was mainly on the basis that there were reports of rare but serious side effects associated with the use of co-trimoxazole, particularly in the elderly. However, the BNF states that the results of post-marketing surveillance have shown no difference in the rate of serious side effects between trimethoprim and co-trimoxazole.6 The BNF also recommends that co-trimoxazole should be reserved for treating HIV-positive patients who are infected with Pneumocystis carinii. Although it has been shown to be the most cost-effective option, its benefit over trimethoprim alone may be small and it is reasonable to follow the BNF recommendation that trimethoprim is more suitable for first-line treatment.
Patients prescribed amoxicillin are significantly more likely to return for a further course of antibiotics than those prescribed trimethoprim. There seems to have been a move away from using amoxicillin as first-line treatment, although it was still the third most frequently prescribed antibiotic for urinary infections (Table 2). The difference in failure rates is statistically significant but perhaps with a NNT of 45, this is not clinically significant. It should be remembered that 50% of patients are unlikely to have had a bacterial infection and the difference in failure rates in patients with a proven bacterial infection may be higher.
There is an increasing move towards the use of cephalosporins, particularly cefalexin, for first-line treatment of urinary infections. Failure rates were significantly greater for patients receiving cefalexin compared with those treated with co-trimoxazole, and there was no evidence that cefalexin was any more effective than trimethoprim (Table 3). Indeed, results for RCTs indicate that failure rates with cephalosporins may be greater than with either co-trimoxazole or trimethoprim.7 The use of the quinolones norfloxacin and ciprofloxacin accounts for <3% of prescriptions. We have shown no difference in failure rates between these products and trimethoprim. There is no support from these findings for using any of these more expensive antibiotics in the first-line treatment of UTIs. They should be reserved for more appropriate clinical situations.
A number of previous studies have shown that short courses of 3 days of antibiotics are as effective as longer courses in uncomplicated UTI.1719 This is supported by the findings of this study where there was no evidence that treatment failure rates differed between patients treated with trimethoprim for 3, 5 or 7 days (Table 6).
This study was retrospective and patients were not randomized between treatments. It is possible, therefore, that the duration of treatment or the antibiotic prescribed reflected symptom severity rather than the arbitrary preferences of individual GPs. However, the increasing use of 3 day treatments of trimethoprim, and the associated reduction in 7 day prescriptions between 1992 and 1999, show that there has been a change in practice (Table 5). It is unlikely that this change is related to a reduction in the severity of the disease over time but is more likely to reflect an evidence-based change in prescribing preferences. Including year of prescribing within the analyses revealed no evidence of changes in failure rates within any duration or antibiotic class during the study period. This finding is inconsistent with the suggestion that preferential prescribing is taking place routinely, and suggests instead that the comparisons between treatment durations or antibiotics are valid.
This study gives doctors some observational evidence of the effectiveness of antibiotic prescribing in young women with UTIs and suggests that whichever antibiotic is prescribed, between 12% and 16% will return within 28 days for a further course of treatment.
We would suggest that 3 days of treatment with trimethoprim appears as effective as 5 or 7 days in everyday practice and we would support this as the preferred option for uncomplicated UTIs in young women.
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Notes |
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References |
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Received 15 January 2001; returned 8 May 2001; revised 6 July 2001; accepted 23 August 2001