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Journal of Antimicrobial Chemotherapy (2007) 59, 1200 – 1203doi:10.1093/jac/dkm108Advance Access publication 21 April 2007 An observational study of empirical antibiotics for adult women with Kathryn O’Brien1*, Sharon Hillier1, Sharon Simpson1, Kerenza Hood2 and Christopher Butler1 1Department of Primary Care and Public Health, Cardiff University, 3rd Floor Neuadd Meirionnydd, Heath Park,Cardiff CF14 4XN, UK; 2South East Wales Trials Unit, Neuadd Meirionnydd, Heath Park, Cardiff CF14 4XN, UK Received 3 October 2006; returned 12 January 2007; revised 16 March 2007; accepted 21 March 2007 Objectives: Women presenting in primary care with symptoms suggestive of uncomplicated urinarytract infection (UTI) are commonly managed without urine culture. We therefore do not know how suc-cessful general practitioners (GPs) are at targeting antibiotic treatment to women who would have hada microbiologically confirmed UTI, or at avoiding antibiotics in those who would have had a negativeculture, had all patients with a suspected UTI been sampled. We therefore explored the associationbetween antibiotic prescribing and urine culture results when culture was performed in all sympto-matic patients.
Methods: GPs in nine general practices in South Wales were asked to submit urine specimens from allwomen consulting with clinically suspected, uncomplicated UTI. Patients were followed up 2 weekslater by questionnaire.
Results and conclusions: One hundred and thirteen adult women with a median age of 54 years wereincluded and 61% received empirical antibiotics. There was very low agreement between the decisionto prescribe empirically and subsequent culture result (Kappa 5 0.04), with 60% of those prescribedempirical antibiotics subsequently found to have a negative culture, and 25% of those found to have apositive culture not prescribed empirical antibiotics. Current strategies to target empirical antibioticprescribing in clinically suspected, uncomplicated UTI require review.
Keywords: urinary tract infections, cystitis, urine culture, empirical antibiotics would have had a microbiologically confirmed UTI, or at avoid-ing antibiotics in those who would have had a negative culture, Clinically suspected, uncomplicated urinary tract infections had all patients with a suspected UTI been sampled.
(UTIs) in adult women are common in general practice, yet the The aim of this study was to explore the extent to which most appropriate strategy for diagnosis and management is not empirical antibiotic treatment turned out to be appropriate, clear.1 Urinary culture is currently considered the gold standard based on subsequent urine culture results in a sample of for diagnosing a UTI. Studies have explored the performance of systematically investigated women with a clinically suspected dipsticks, microscopy and symptom scores in predicting culture results.2 – 4 A recent meta-analysis found a large variation in thediagnostic accuracy of dipsticks, further illustrated by two sub-sequent studies in primary care.3,5,6 Several clinical scoring systems have been proposed. However, clinical scores, evenwhen enhanced with results of dipstick tests, have poor predic- This exploratory study was nested within a larger study examining tive value.5 – 8 General practitioners (GPs) employ a range of the epidemiology, aetiology and outcomes of antibiotic-resistant, strategies to aid diagnosis and management of suspected UTI.2 community-acquired UTI.9 Ten general practices in South East Currently, urine samples are not routinely sent for culture on all Wales were recruited from within the former Bro Taf Health those with suspected UTIs. It is therefore not known how suc- Authority. All practices in this region were originally stratified by cessful GPs are at targeting antibiotic treatment to women who quartiles for prescribing rates, size, Townsend deprivation score and . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
*Corresponding author. Tel: þ44-29-2068-7173/029-2068-7148; Fax: þ44-29-2068-7219; E-mail: obrienka@cf.ac.uk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
# The Author 2007. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
For Permissions, please e-mail: journals.permissions@oxfordjournals.org Observational study of empirical antibiotics for adult women historical rate of submitting urine samples. Five practices alreadyparticipating in surveillance work were invited to participate, and afurther five were selected to ensure a balance across these par-ameters. One practice declined to participate and was replaced witha nearby practice with a similar profile. Results from nine of theseten practices were included in our analysis as the laboratory resultswere temporarily unobtainable for one of the practices due to techni-cal difficulties. The total population across the nine practices was64 872, including 26 704 women aged 18 years and over.
Patients were recruited during the last month of the larger study (1 – 31 March 2004). Clinicians were asked to recruit all eligiblepatients, aged 18 and over, with a clinically suspected uncompli-cated UTI. The clinicians explained the study to eligible patients,obtained written informed consent, and requested a urine samplefrom all patients for laboratory analysis. They were then asked tomanage the patients according to their usual practice (no additionalguidelines were given on the management of suspected UTI).
Women who required immediate hospitalization for suspected pyelonephritis were not included in the study, but women managed inthe community were not excluded on the basis of symptoms such as Figure 1. Response rates and exclusions.
fever or back pain. Women with no symptoms consistent with a UTIand those with underlying renal and bladder problems, in-dwellingcatheters, a history of UTI in the preceding month, current pregnancy hundred and twelve urine specimens were submitted from the or insulin dependent diabetes mellitus were excluded on the basis of nine GP practices during the study month. Of these 152 were information given on their questionnaire.
specimens from males, 79 were from females aged ,18 years, Specimens were sent to local laboratories using routine transport 36 were duplicate specimens, 6 had missing demographic infor- systems and were examined there using standard operating pro- mation and 51 specimen results were not received by the cedures (Cardiff Public Health Laboratory and Royal Glamorgan Hospital, Llantrisant). Paper copies of the laboratory results forthese specimens were sent to the research team at the same time as Questionnaires were sent to the remaining 288. Exclusions and they were sent to the practices. A threshold of .105 organisms per response rate are presented in Figure 1.
mL defined a positive culture. Questionnaires and further study Two eligible cases were excluded from the analysis; one had information were sent to consenting patients within 2 weeks of the independently submitted a urine sample to the laboratory where research team receiving the laboratory results. Patients were asked she worked and presented to her GP with a positive culture when they saw the nurse or GP, whether they were prescribed anti- result, and we were unable to obtain adequate information about biotics or not, and if so, when. Additional questions were included antibiotic prescribing in the other case. The remaining 111 in order to exclude non-eligible patients. We used a modified women contributed data to the analysis.
version of the questionnaire used in the larger study, which had There was no difference in the proportion of culture positive been piloted. The questionnaire was either self completed and urine between those who completed a questionnaire and non- returned by post, completed over the telephone, or completed face to face with one of the researchers. A reminder slip and one further younger (median age 44, IQR 30 – 64) compared with responders questionnaire were sent to non-responders 2 weeks after the first (median age 54, IQR 34 – 71), however this difference was not questionnaire. Antibiotic prescribing was confirmed by contacting statistically significant (Mann – Whitney U ¼ 5521, P ¼ 0.122).
surgeries in those cases where there was insufficient or conflicting Table 1 shows the association between antibiotic prescription Data were entered into Excel, cleaned and coded, and then trans- Antibiotics were prescribed empirically in 61% (68/111) ferred into SPSS for analysis. Comparison of groups was carried out cases. Of those prescribed empirical antibiotics, 40% (27/68) using non-parametric tests as the data were skewed. x2 and Mann – were subsequently found to have a positive urine culture and Whitney U-tests were used to compare responders and non- 60% (41/68) were found to have a negative culture.
responders. Agreement between empirical prescribing and urinary Overall, 32% (36/111) had a positive culture. Seventy-five culture was assessed using a Kappa statistic. Assessment of thedirection of disagreement was undertaken using the McNemar x2.
percent (27/36) of these women had been prescribed antibiotics Percentages are presented to the nearest whole number.
Ethical approval was granted for this study by the South East Wales Local Research Ethics Committee.
Table 1. Association of empirical antibiotic prescription with urineculture result Empirical decision by GP Positive culture Negative culture Total There was an increase of 24% in total urine specimens sub- mitted from all study practices during the period of the main study (average of 6505 per year in the year preceding the study, and an average of 8059 per year during the main study). Six empirically, whereas 25% (9/36) had not. Of the 68% (75/111) 44 years. Other studies have used an upper age limit, sometimes of women who had a negative culture result, 55% (41/75) had as low as 50 years.4,6,11,12 In our study, the prevalence of posi- been prescribed empirical antibiotics.
tive urine culture in clinically suspected UTI was 32%. This is The decision to prescribe empirical antibiotics against the lower than in other similar studies, although estimates of preva- target of a positive urine culture had a sensitivity of 75% (95% lence vary widely amongst studies.2,4,7 The lower prevalence CI 61287%), specificity of 45% (95% CI 38251%), positive may also be a reflection of the systematic sampling method used predictive value of 40% (95% CI 32246%) and a negative predictive value of 79% (95% CI 67289%).
An important aspect of our study was that health pro- The Kappa measure of agreement showed very low agree- fessionals were asked to request specimens from all patients ment between the decision to prescribe empirical antibiotics and with clinically suspected UTI. However, the extent to which this subsequent culture result (Kappa ¼ 0.04).
happened was not easily validated, as practices were not able to Of the 50 (45%) women where there was disagreement keep a log of all patients presenting with UTI symptoms. There between empirical prescribing and urinary culture, significantly was an overall increase of 24% in the number of urine samples more had been prescribed antibiotics and subsequently had sent by practices during the main study period. Extrapolating a negative culture (82%) than vice versa (18%) (x2 ¼ 19.220, from our data for 1 month, in which 288 samples were sub- mitted from a population of 26 704 women aged 18 or over, weestimate the annual consulting rate for suspected UTI of 13%,assuming a sample was requested in every case. This estimate is similar to findings in other studies.7,13 Further research is needed to explore the cause of symptoms It is commonly accepted that patients with symptoms attribu- in patients with negative urine cultures, to clarify which patients table to the urinary tract and who have a positive culture are with symptoms suggestive of UTI are most likely to benefit most likely to benefit from antibiotics. The research effort has from antibiotics, and to develop strategies to treat these patients focused on developing management strategies to predict positive while continuing to address unnecessary antibiotic prescribing in culture more reliably in order to better target antibiotic prescrib- the light of the problem of antibiotic resistance.
ing.2,3,10 Our findings suggest that current management strategiesare not achieving this goal. Culture positive UTI was not pre-dicted by the empirical decision to prescribe antibiotics. The specificity was low, and the sensitivity was fairly low. GPs weremore likely to prescribe empirically for those subsequently We thank Professor Stephen Palmer, PI of the main Wellcome found to have a negative culture than to have not prescribed for Trust Funded study (grant number GR064010MA) and Dr those who are subsequently found to have positive culture. It Anthony Howard and colleagues for the opportunity and support remains unclear which subgroup of patients will benefit from to conduct this related research. We thank the patients and the antibiotics, and in which (if any) antibiotic treatment will not be participating general practices and laboratories who contributed worthwhile. A recent study found that patients with negative to this research, and Mrs Suzie Horan who conducted interviews culture received some benefit from antibiotic treatment.11 However, other studies have shown that many UTIs are self-limiting, improving without treatment even when culture is posi-tive.12 Empirical antibiotics for all those with symptoms of UTImay be the best policy.2,11 Our results may be a reflection that some practitioners are adopting a strategy of prescribing empiri- cal antibiotics for all patients, and have perhaps been influencedby evidence suggesting that antibiotics may benefit some womenwith suspected UTI who have culture negative urine. The issueof antibiotic resistance also needs to be taken into account when considering which strategy to promote. A recent review paperhighlights the fact that the most appropriate management 1. PRODIGY Guidance. Urinary Tract Infection (Lower)—Women.
Limitations of this study include possible response bias, small sample and the reliance on patient recall of antibiotic 2. Hummers-Pradier E, Ohse AM, Koch M et al. Management of urinary tract infections in female general practice patients. Fam Pract treatment in the majority of cases. Responders and non- responders to the questionnaire had similar proportions of posi- 3. Deville´ W, Yzermans J, van Duijn N et al. The urine dipstick test tive urine cultures, and there was no statistically significant useful to rule out infections. A meta-analysis of the accuracy. BMC difference in their ages. We were not able to make judgements about comparability of symptom severity, rates of antibiotic pre- 4. McIsaac WJ, Low DE, Biringer A et al. The impact of empirical scribing and outcomes between these groups. With a median age management of acute cystitis on unnecessary antibiotic use. Arch of 54, our study participants were older than we expected, although they were of a similar age to participants of a recent 5. Little P, Turner S, Rumsby K et al. Developing clinical rules to study in Germany (median age 53 years).2 Participants in other predict urinary tract infection in primary care settings: sensitivity and studies have tended to be younger. For example participants in a specificity of near patient tests (dipsticks) and clinical scores. Br J Gen Canadian study, with no upper age limit, had an average age of Observational study of empirical antibiotics for adult women 6. Nys S, van Merode T, Bartelds A et al. Urinary tract infections in general practice patients: diagnostic tests versus bacteriological Randomised controlled trial of nitrofurantoin versus placebo in the culture. J Antimicrob Chemother 2006; 57: 955 – 8.
treatment of uncomplicated urinary tract infection in adult women. Br J 7. Bent S, Nallamothu BK, Simel DL et al. Does this women have an acute uncomplicated urinary tract infection? JAMA 2002; 287: 11. Richards D, Toop L, Chambers S et al. Response to antibiotics of women with symptoms of urinary tract infection but negative dipstick 8. Fahey T, Webb E, Montgomery AA et al. Clinical management urine test results: double blind randomised controlled trial. BMJ 2005; of urinary tract infection in women: a prospective cohort study. Fam 12. Ferry S, Holm S, Stenlund H et al. The natural course of 9. Butler CC, Hillier S, Roberts Z et al. Antibiotic-resistant infec- uncomplicated lower urinary tract infection in women illustrated by a ran- tions in primary care are symptomatic for longer and increase work- domized placebo controlled study. Scand J Infect Dis 2004; 36: 296–301.
load: outcomes for patients with E. coli UTIs. Br J Gen Pract 2006; 56: 13. Car J. Urinary tract infections in women: diagnosis and manage- ment in primary care. BMJ 2006; 332: 94– 7.

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