Recurrent urinary tract infections in women with symptoms of pelvic floor dysfunction

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1 Int Urogynecol J (2009) 20: DOI /s ORIGINAL ARTICLE Recurrent urinary tract infections in women with symptoms of pelvic floor dysfunction Bernard T. Haylen & Joseph Lee & Sue Husselbee & Matthew Law & Jialun Zhou Received: 5 December 2008 /Accepted: 1 March 2009 /Published online: 17 March 2009 # The International Urogynecological Association 2009 Abstract Introduction and hypothesis The prevalence and clinical associations of recurrent (two or more symptomatic and medically documented in the previous 12 months) urinary tract infections (UTIs) have not been subjected to comprehensive analysis in a large group of women with symptoms of pelvic floor dysfunction. Methods A prospective study was conducted involving 1,140 women presenting for their initial urogynecological assessment. Results The overall prevalence of recurrent UTI was 19%. Significant positive associations of recurrent UTI were: (1) nulliparity with a 3.7 (up to 50 years) increase over the prevalence for parous women and 1.8 (over 50 years); and (2) women with an immediate postvoid residual (PVR) over 30 ml, which is significant in women over 50 years. Conclusions The early age decline (18 45 years) in the prevalence of recurrent UTI might be related to increasing parity. The later increase (over 55 years) was probably due to the increasing PVR effect superimposed on the nulliparity effect. B. T. Haylen (*) : S. Husselbee St Vincent s Clinic, Suite 904, 438 Victoria Street, Darlinghurst 2010 NSW, Australia haylen@optusnet.com.au J. Lee Mercy Hospital, Melbourne, Victoria, Australia M. Law : J. Zhou National Centre in HIV Epidemiology & Clinical Research, University of New South Wales, Kensington, NSW, Australia Keywords Pelvic floor dysfunction. Recurrent urinary tract infections. Prolapse. Postvoid residual. Ultrasound. Urodynamics Introduction Around 40% of women will have a urinary tract infection (UTI) sometime in their life and 27% will have a recurrent UTI within 6 to 12 months [1]. There is no clear and universally accepted definition for recurrent UTIs. Proposed definitions have included two or more [2], three or more [3], andfourormore[4] UTIs in the previous 12 months. There is no scientific evidence to support one particular definition. Recurrent UTIs, using the literal meaning of recur, namely to occur again or be repeated, is defined here as at least two symptomatic and medically documented UTIs in the previous 12 months. Recurrent UTIs have not been subjected to comprehensive study in a large cohort, across all age groups, for their relationship to a wide range of clinical and urodynamic parameters. Previous discussion of risk factors for recurrent UTI in women has tended to be separated [5] on the basis of age into (a) healthy young premenopausal women, (b) healthy menopausal women between 50 and 70 years, and at times, (c) the third category of elderly women (with a subcategory of those who are institutionalized). The cohorts for most studies to date have reflected that separation. Factors implicated to date in young women with recurrent UTI are (a) sexual intercourse [5 7], including a new sexual partner in the previous year [6]; (b) contraceptive use, particularly the use of spermicides, diaphragms, and oral contraceptives [5, 6, 8, 9]; (c) familial predisposition [10]; and (d) distance from the urethra to the anus

2 838 Int Urogynecol J (2009) 20: [11]. Other studies have focused on (e) the increased susceptibility of women with recurrent UTI to vaginal colonization with uropathogens compared with women without a history of recurrent UTI [12]; and (f) a three to four fold increase prevalence of recurrent UTI in women who are non-secretors of ABO histo-blood group antigens (uropathogenic Escherichia coli adhere better to uroepithelial cells from women who are non-secretors) [13]. In postmenopausal women, factors associated with recurrent UTI have been reported to include: (g) a premenopausal history of UTI, (h) estrogen deficiency, (i) urogenital surgery, (j) cystocoele, (k) high postvoid residual (PVR), and (l) prior UTI [14, 15]. A high PVR and the potential beneficial effect of estrogen replacement have been highlighted in elderly women with recurrent UTI [2]. This study aims to present data for a large cohort of women with symptoms of pelvic floor dysfunction, over all adult age groups (from under 20 to over 90 years), all receiving the same extensive assessment. Only then, can the prevalence, associations, and age relationships of recurrent UTI in this cohort be properly determined. Materials and methods The study involved 1,140 women, all of whom were consecutive referrals for an initial routine urogynecological assessment including urodynamics because of symptoms of pelvic floor dysfunction. All women gave informed consent to undergo the assessment and to be included in the study. Assessments occurred from December 2002 to June None had a known or suspected current UTI or were using any form of catheterization. As part of a comprehensive history, each woman was questioned specifically on the exact number of symptomatic and medically documented UTI in the previous 12 months. A full examination was then performed. Initial testing for clinical stress leakage was by coughing in the supine and standing positions with the presenting bladder volume. Prolapse assessment followed voiding (for uroflowmetry) to eliminate the effect of a full bladder restricting the full extent of the prolapse [16]. Separate assessments were made for the presence and stage of any uterine prolapse, anterior vaginal wall, posterior vaginal wall, and vaginal vault prolapse. The patients were examined in the left lateral position using a Sims speculum and at maximal strain. Stages 1 and 2 (within 1 cm above or below the hymen) were equivalent to the respective International Continence Society (ICS) stagings [17]; ICS stages 3 and 4 were combined. Uterine version was determined using transvaginal ultrasonography with bladder emptied after micturition. A single investigator performed all the studies. Each woman, having been encouraged to attend for the assessment with a comfortably full bladder, voided for free uroflowmetry in complete privacy over a Urodyn 1000 uroflowmeter (Medtronic, Minneapolis, MN, USA). The maximum and average urine flow rates and the respective voided volumes were recorded. Immediate (within 60 s of voiding) PVRs were measured by transvaginal ultrasonography (UST probe; Aloka, Tokyo, Japan single scan, sagittal image) [18]. Where the PVR was over 175 ml (the upper limit of the transvaginal ultrasound technique), measurement of PVR was by urethral catheterization using a 14-Fr short plastic catheter. This catheter leaves an average bladder volume after catheterization of less than1ml[19]. The initial PVR was used for subsequent analysis, although where the initial PVR was over 10 ml, the patient voided for a second time over a conventional toilet (rather than a uroflowmetry commode) for repeat void PVR analysis. The lowest value was taken as the final PVR. Further urodynamic testing involved the assessment of bladder (detrusor) function, during filling with water and with subsequent micturition (multichannel filling and voiding cystometry). A 7FG dual lumen catheter was used for bladder pressure measurement and filled with water at 75 ml per minute. Data were separated according to the number of UTIs (each woman s self-reporting of the number of symptomatic and medically documented) in the previous year: (a) none or one UTI; (b) two or more UTI. Factors associated with recurrent UTI were assessed using multiple logistic regression. These included age, parity, presenting symptoms, prior hysterectomy, menopause/hrt use, previous continence surgery, all grades of prolapse as well as all the final urogynecological diagnoses. Because initial analyses indicated important interaction effects between age and other certain factors, analyses were stratified according to age (50 years and under; over 50 years). The definitions of the symptoms of stress and urge incontinence were in line with ICS definitions [17]. Prolapse symptoms were present if the woman said yes to any of the following: (a) the sensation of pelvic pressure, (b) a vaginal bulge, or (c) something falling down in the vagina. Symptoms of voiding difficulty involved a yes to any of the following: (a) hesitancy, (b) a poor stream, (c) the need to strain to void as single symptoms, or (d) the combination of symptoms of the sense of incomplete emptying and the need to immediately revoid. Other final diagnoses sought (apart from prolapse already mentioned) were: (a) urodynamic stress incontinence (USI); (b) detrusor overactivity (DO); (c) sensory urgency (bladder oversensitivity), defined as an increased perceived bladder sensation during filling, a low first desire to void (generally under 100 ml), and a low maximum

3 Int Urogynecol J (2009) 20: cystometric bladder capacity (under 400 ml in a predominantly Caucasian population) in the absence of recorded current or recent urinary UTI or detrusor overactivity [20]; voiding dysfunction [21] (abnormally slow urine flow rate [under the 10th centile Liverpool nomogram; 22] and/or a high immediate PVR [over 30 ml]). Urine flow rates need to be corrected to allow for their strong dependency on voided volume. Each urine flow rate and the respective voided volume were thus applied to the equation form of the Liverpool nomograms [22] to obtain a centile ranking. Only flow data (maximum urine flow rate) from within the range of interpretation of the Liverpool nomograms (voided volumes ml) were included in this part of the analysis. Analysis was performed using the STATA statistical package (STATA 8.2 for Windows, StataCorp LP, College Station, TX, USA). Factors that are associated more than one UTI in the last 12 months were assessed using multivariate logistical regression models with a forward stepwise approach. The final multivariate model included only covariates that remained significant at the 0.05 level (two-sided). Because this study, which requires no departure from routine practice, conforms to the standards established by the Australian National Health & Medical Research Council ( pdf; pages 18, 79) for ethical quality review, full ethics review was not deemed to be required. The Institutional Ethics Committee confirmed this exemption. Results The overall prevalence of recurrent UTI was 19%. Table 1 shows the distribution of the different numbers of symptomatic and medically documented UTIs in the previous 12 months. Using three or more or four or more UTIs as the definition for recurrent UTI, the cohort would have been Table 1 The distribution of the different numbers of symptomatic and medically documented UTIs in the previous 12 months Number of UTI Frequency Percent Cumulative More than Total 1, reduced to 11% and 8%, respectively. Subsequent analysis and discussion was performed on the cohort of women with two or more UTIs in the previous 12 months. Median age for the overall group was 58 (range 18 98); median parity was 2 (range 0 9). The prevalence for the other urogynecological diagnoses was USI (72%), uterine and/or vaginal prolapse (64%), voiding dysfunction (36%), detrusor overactivity (23%), and sensory urgency (bladder oversensitivity) (10%). In women 50 years and under, there was a trend of decrease in the prevalence of recurrent UTI (p=0.155). In women over 50 years, there was a trend of increase in the prevalence (also not statistically significant, p=0.052). The difference between these two trends was significant, p= 0.001, leading to a quadratic curve as shown in Fig. 1. Table 2 shows further analysis of dividing the data for the cohort into (a) women 50 years or under and (b) women over 50 years. The most notable associations with recurrent UTI in the multiple logistic regression were nulliparity and a PVR over 30 ml. Nulliparous women of all ages have a significantly higher prevalence of recurrent UTI: for women 50 years and under odds ratio 3.7 (p<0.001); for women over 50 years odds ratio 1.8 (p=0.047). There appears to be a possible protective effect of parity, which was stronger in younger women than in older women (p=0.008). Recurrent UTIs increase significantly with the increase in PVR (over 30 ml) for women over 50 years (p=0.018). The small number of women 50 years and under with a PVR over 30 ml probably contributed to a less significant relationship (p=0.056) in this group. The other positive relation of recurrent UTI in women over 50 years is the final diagnosis of voiding dysfunction (p=0.040), which incorporates a high PVR (over 30 ml) into its definition. Factors negatively associated with recurrent UTI, all for women over 50 years, are vaginal hysterectomy (p=0.002), final diagnosis of DO (p<0.001), and final diagnosis of prolapse (stage 3 [stages 1, 2 non-significant inverse relation] prolapse vs. stage 0 prolapse: p=0.001). There were no significant associations between recurrent UTI and the use/non-use of hormone replacement therapy (p=0.658), prior abdominal hysterectomy (p=0.126), prior continence surgery (p=0.501), the retroverted uterus (p=0.366), or the final diagnoses of urodynamic stress incontinence (p=0.639) or sensory urgency (bladder oversensitivity; p=0.083). Table 3 shows the different PVR levels separated according to the number of UTI in the previous 12 months: (a) none or one UTI; (b) two or more. As already noted, there is an increase in recurrent UTI with increasing PVR. The level of 30 ml appears to be the most appropriate upper limit of normal PVR from which recurrent UTIs are seen to increase, compared to a PVR level of 50 ml (by receiver

4 840 Int Urogynecol J (2009) 20: Fig. 1 The prevalence of (a) two or more UTIs (previous 12 months) and (b) none or one UTI (previous 12 months) with age % ~25 26~35 36~45 46~55 56~65 66~ Age (years) UTI: 0~1 UTI: 2 or more operating characteristics [ROC] analyses, ROC area [PVR=30 ml] vs [PVR=50 ml], p=0.067, [we cannot say which is absolutely better, since the p value is not less than 0.05]). Discussion Nulliparity and a PVR over 30 ml are the significant positive associations for an increased prevalence of recurrent UTI Table 2 Factors associated with the history of two or more UTI in the previous 12 months stratified by age: (1) 50 years and under; (2) over 50 years Previous 12 months No. of patients No. of UTI 2 (%) Adjusted OR (95% CI) p value No. of patients No. of UTI 2 (%) Adjusted OR (95% CI) p value p value + Age 50 years (n=351) Age > 50 years (n=789) Age 0.77 ( ) ( ) (per 10 years) Parity (14%) 1.00 Ref (25%) 1.00 Ref Nulliparous (46%) 3.71 ( ) < (34%) 1.80 ( ) Prolapse S (32%) 1.00 Ref (25%) 1.00 Ref Prolapse S (11%) 0.39 ( ) (33%) 1.17 ( ) Prolapse S (12%) 0.50 ( ) (23%) 0.72 ( ) Prolapse S (0%) (17%) 0.29 ( ) PVR 30 ml (20%) 1.00 Ref (23%) 1.00 Ref PVR >30 ml 29 9 (31%) 2.49 ( ) (34%) 1.93 ( ) Prev Abdo Hyst 22 3 (14%) 1.00 Ref (32%) 1.00 Ref No hysterectomy (22%) 1.41 ( ) (25%) 0.73 ( ) Prev Vag Hyst 17 1 (6%) 0.69 ( ) (14%) 0.29 ( ) No DO (21%) 1.00 Ref (28%) 1.00 Ref DO (22%) 0.73 ( ) (17%) 0.37 ( ) < No VD (19%) 1.00 Ref (21%) 1.00 Ref Voiding dysfunction (30%) 1.65 ( ) (31%) 1.66 ( ) S stage, PVR postvoid residual, Prev previous; Abdo Hyst abdominal hysterectomy, Vag Hyst vaginal hysterectomy, DO detrusor overactivity

5 Int Urogynecol J (2009) 20: Table 3 The different PVR levels separated according to the number of UTIs in the previous 12 months: (a) none or one; (b) two or more UTI in the previous 12months PVR PVR PVR PVR PVR Total 0 10ml 11 30ml 31 50ml ml Over 100ml None or one % 87.10% 69.81% 73.63% 73.13% 81.32% 2 or more % 12.90% 30.19% 26.37% 26.87% 18.68% Total % % % % % % This table is reproduced with kind permission from Wolters Klewer Health, Baltimore [24] in women. Through the influence of a high PVR in the determination of the diagnosis of voiding dysfunction, it is not surprising that diagnosis also has a significant positive association. This appears to be the first time that nulliparity and recurrent UTI have been so clearly linked. The corollary is that parity may possibly be protective for recurrent UTI. The sexual factors cited [5 9] as possible contributors to recurrent UTI might change with parity, e.g., number of partners. Detailed and accurate sexual histories have proven to be difficult for researchers. The burdens of new motherhood or other later family issues might be reflected in a decreased frequency of intercourse. The significance of parity as a factor might indicate that the relaxant or stretching effect of pregnancy and/or parturition on the birth canal might be of positive benefit in preventing recurrent UTIs. If the frictional effect of intercourse on the lower urinary tract is a causative factor for recurrent UTI, then this effect might well be reduced. The other clear factor is a high PVR (over 30 ml). O Grady and Cattell [23] pointed to 30 ml as the level of PVR at which recurrent UTI become more frequent. This level has been proposed and supported as the upper limit of normal PVRs by the above measurement technique. Below this level are 81% and 87% of PVRs in symptomatic women [24, 25]. These data support an upper limit of normal PVR of 30 ml if measured by suitably accurate ultrasound immediately after micturition. A PVR assessment, generally by ultrasound, is recommended as an appropriate investigation for women with recurrent UTI. There was an increased chance of recurrent UTI with a final diagnosis of voiding dysfunction (p=0.040), which incorporates urine flow rate, PVR, and voiding cystometry data. A preliminary diagnosis of voiding dysfunction, defined [21] as abnormally slow and/or incomplete micturition, has been shown to occur in up to 39% women attending for urogynecological assessment [26]. Subsequent voiding cystometry is required to confirm the final diagnosis and a possible cause. One finds it initially difficult to explain the increasingly (with higher grade) negative association of prolapse and recurrent UTI. A clear link between prolapse and voiding dysfunction has already been demonstrated [26]. Here, there is a clear link between recurrent UTI and voiding dysfunction, yet an inverse relationship between recurrent UTI and prolapse. A possible explanation is that recurrent UTIs are far more likely in nulliparous women and prolapse is far more likely in parous women where any stretching effects of childbirth are clearly further exacerbated. Pelvic organ prolapse appears to also have a negative impact on sexual function [27]. A history of recurrent UTIs is relatively common (19%) among women attending with symptoms of lower urinary tract dysfunction. This figure and the other data enclosed are consistent with previous reports that between 10% and 35% of women will suffer recurrence of their UTI [1, 28] and that 2 10% of women will have multiple recurrences [28]. This study has been conducted on a specific, generally healthy female cohort rather than at random. The main reasons for urogynecological referral, namely urinary incontinence and prolapse, are common with respective prevalences among women of around 35% [29] and up to 50% [30], respectively. Because of the first visit nature of the consultation, a detailed sexual history was not taken. The ethical exemption (no departure from routine practice) precluded exploration of possible medical confounders. Additional research is required, therefore, to focus on specific sexual and medical confounders. While the diagnosis of recurrent UTI is seen to have no overall significant age relationship, Fig. 1 demonstrates a peak in women under 25 decreasing to the lowest levels at age before rising again to a second peak in women over 75 years. It is postulated that the early decline can be explained by increasing parity while the late increase might be related in part to an ongoing but smaller influence of parity and an increasing PVR from whatever cause. The study is limited by the accuracy of patient-reported history of recurrent urinary tract infections though this

6 842 Int Urogynecol J (2009) 20: might apply to many studies involving elements of history. Time was taken to assist patient recall of each episode of UTI to confirm, in particular, that it had been medically documented. Relevant investigations varied and the results were frequently unavailable. The cohort was a subspecialty population referred for pelvic floor dysfunction including pelvic organ prolapse, urinary incontinence, and voiding problems rather than women presenting for an annual examination in a gynecological clinic. The study illustrates, however, that recurrent UTI is a significant diagnosis in the group. Conflicts of interest References None. 1. Foxman B (1990) Recurrent urinary tract infections: incidence and risk factors. Am J Public Health 80: Stern JA, Hsieh YC, Schaeffer AJ (2004) Residual urine in an elderly female population: novel implications for oral oestrogen replacement and impact on recurrent urinary infections. 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