European Geriatric Medicine 3 (2012) 87–91
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Research paper
Asymptomatic bacteriuria among the elderly living in the community: Prevalence, risk factors and characteristics M. Varli a,*, H. Guruz b, S. Aras a, A. Yalcin a, T. Atli a, M. Turgay a a b
Department of Geriatric Medicine, Ankara University School of Medicine, Cebeci, Ankara 06110, Turkey Department of Clinical Microbiology, Ankara University School of Medicine, Cebeci, Ankara 06110, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history: Received 23 September 2011 Accepted 2 January 2012 Available online 28 February 2012
Background: Asymptomatic bacteriuria (ASB) is common among the older persons. Several factors may precipitate ASB, including age-related changes in genitourinary system and comorbid diseases. Unnecessary antibiotic use for ASB could be associated with increased antibiotics resistance. The aim of this study was to determine the prevalence and related factors of ASB among the elderly living in the community. Methods: In this study, 625 patients admitted to our geriatric outpatient clinic were enrolled. Comprehensive geriatric and physical assessment, a standardized questionnaire, medical history, and urine and blood sampling were performed. ASB was defined as identical microorganisms isolated from two consecutive urine specimens ( 105 colony-forming units/mL). Results: Mean age of patients was 72.4 5.6 and 394 (63%) were female. The prevalence of ASB was 6.2%. Whereas female gender was associated with ASB, presence of ASB was not associated with age, previous urinary tract infection (UTI), urolithiasis, genitourinary surgery, and/or urinary incontinence. Similarly, diabetes mellitus (DM), obesity, hypertension, and creatinine clearance were not found to be associated with presence of ASB. Laboratory results were similar in the subjects with or without ASB. The most commonly isolated organism was Escherichia coli (66.7%). In addition, while the specificity of leukocyte-esterase and nitrite were high, the sensitivity of both tests was low in the subjects with ASB. Conclusions: These results indicate that ASB is common and the main risk factor for ASB is female gender among non-institutionalized elderly. E. coli were the most commonly isolated bacterium. Urine dipstick tests seem to be useful in older persons to exclude the presence of bacteriuria. ß 2012 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
Keywords: Asymptomatic bacteriuria Community Elderly Prevalence Risk factors
1. Introduction Asymptomatic bacteriuria (ASB) is common both in the community-dwelling and institutionalized elderly [1]. However, its prevalence varies widely with age, gender, multiple comorbid diseases and age-related physiological changes in genitourinary tract in older persons [2]. The prevalence of ASB increases with advancing age in subjects older than 65 years and ranges from 6% to 16% in women and 5% to 21% in men. On the other hand, among the institutionalized elderly, 25% to 50% of women and 15% to 35% of men have ASB [3]. The clinical significance of ASB in the elderly is not clear [4]. However, it is usually known as a benign condition [5]. Reason of ASB in the elderly is multifactorial and complex [6]. Some studies have indicated an association between ASB and urinary incontinence, hypertension and decreased renal function. Similarly,
* Corresponding author. Tel.: +90 312 5957922; fax: +90 312 3623441. E-mail address:
[email protected] (M. Varli).
diabetes mellitus (DM), especially poor glycaemic control, may precipitate ASB, but their relation and clinical implications are not well defined [7–9]. The diagnosis of ASB is based on the result of a urine culture from a urine specimen. Bacteriuria is defined as the presence of two consecutive clear-voided urine specimens with isolations of the same bacterial strain in quantitative counts of 105 colonyforming units (CFU) per mL. Pyuria is evidence of inflammation in the genitourinary tract and is common in subjects with ASB [10]. Moreover, dipstick urinalysis is often the first evaluation for detection of bacteriuria and pyuria. However, different combinations of the dipstick urinalysis improve the diagnostic value [11]. Although the high prevalence of bacteriuria is associated with urinary incontinence, impaired functional status, and chronic comorbid illnesses in elderly institutionalized people, [5] few studies have been performed investigating related risk factors for ASB in elderly living in the community. The aim of this study was to investigate the prevalence of ASB, and to identify associated factors with ASB among the elderly living in the community.
1878-7649/$ – see front matter ß 2012 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved. doi:10.1016/j.eurger.2012.01.007
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M. Varli et al. / European Geriatric Medicine 3 (2012) 87–91
2. Subjects and methods 2.1. Subjects A total of the 2968 patients aged 65 and older who were admitted to the outpatient clinic of the Department of Geriatric Medicine at Ankara University Cebeci Hospital, for comprehensive geriatric assessment between January 2004 and May 2006 were included in this cross-sectional study. The majority of the participants were living in Ankara, the capital city of Turkey, and the surrounding area. Patients were included only once. Of the patients, 921 (31%) declined participation. All patients underwent a complete geriatric assessment. Exclusion criteria were symptoms of a urinary tract infection (UTI) (e.g. fever, dysuria, frequency, urgency, gross hematuria, or suprapubic pain), recent hospitalization or surgery (within the past 3 months), the use of antimicrobial drugs in the past months, institutionalized elderly, subjects with urinary catheter, known anatomic urinary tract abnormalities (e.g. cystoceles, hydronephrosis, renal atrophy or neurogenic bladder) and systemic illnesses (e.g. collagen tissue or vascular diseases), infectious diseases and malignancies, which can lead to elevated levels of CRP and sedimentation. Patients unable to give an adequate urine specimen and sufficient information due to functional impairment and/or dementia and patients who had contamined urine specimens were also excluded. After exclusions according to the exclusion criteria, 625 functionally independent, cognitively intact older persons between the ages of 65 and 93 years (mean 72.4 5.6 years) were enrolled in this study. The study protocol was approved by the local ethics committee. 2.2. Assessment of patients A standardized comprehensive geriatric assessment including the minimental state examination (MMSE) (MMSE < 24 indicate impaired cognition, suggesting dementia) [12], activities of daily living (ADL) (higher scores indicate less ability) [13], instrumental activities of daily living (IADL) (lower scores indicate poorer ability) [14] and the short version of mini nutritional assessment test (S-MNA) (MNA 11 indicate malnutrition risk) were performed [15]. A physical examination, weight, height, body mass index (BMI) and medical history were also obtained in detail. BMI was calculated as the ratio of weight to height squared for each subject. Medical history included self-report of hypertension, DM, coronary artery disease, hyperlipidemia, congestive heart failure, chronic obstructive pulmonary disease, benign prostatic hyperplasia (BPH) and urinary incontinence. Data were obtained using a standardized questionnaire including age, number of UTI within the previous year, parity, genitourinary tract surgery, history of urolithiasis, drug use. The following laboratory values were obtained: fast blood glucose level, serum creatinine level, glycosylated hemoglobin A1c value (HbA1c) (only subjects with DM), C-reactive protein (CRP) level, sedimentation, complete blood count using standard methods. Creatinine clearance was estimated by using Cockcroft-Gault formula: [(140 age) (Weight in kg) (0.85 if female) /serum creatinine 72] [16]. 2.3. Definitions A clean-catch, midstream urine specimens were obtained from all the subjects for urine analysis, microscopy, culture and antimicrobial susceptibility tests. If the first specimen was positive, a second specimen was obtained and cultured within
one week in order to confirm ASB. ASB is defined as two consecutive clean-catch voided urine specimens with isolation of the same bacterial strain in quantitative counts greater than or equal to 105 CFU per mL. Pyuria was defined as a urinalysis that disclosed more than five white blood cells per high-powered field under light microscopic examinations in the sediment of centrifuged urine [1]. Dipstick urinalysis using the Multistix 10 SG reagent strip, (Bayer Corporation) was used for the detection of nitrite production as an indicator of bacteriuria and leukocyte esterase (LE) activity as an indicator of pyuria, with the urine chemistry analyzer Clinitek 100. Positive dipstick was defined as positive to either LE (trace, + or + +) or nitrite (positive). Negative dipstick was defined as negative to both LE and nitrite [17]. Blood agar and eosin methylene blue agar were used for routine urine cultures. Plates were incubated aerobically for 24 h at 37 8C. Organisms were counted and identified by using standard microbiologic methods. Antimicrobial susceptibility testing was performed using the disk diffusion method as described by the National Committee for Clinical Laboratory Standards (NCCLS) [18]. 2.4. Statistical analysis The results are expressed as mean SD or median. The data were analyzed by SPSS statistical software for Windows (version 15.0; SPSS, Chicago, IL, USA). Data were compared using chi-square analysis or Fisher’s exact test for categorical variables and the t-test or MannWhitney U test for quantitative variables, when appropriate. Logistic regression was used to determine the risk factors associated with ASB in the presence or absence of bacteriuria. Risk assessment was measured by odds ratio with a 95% confidence interval. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for nitrite and LE separately using urine culture as gold standard. A P value of less than 0.05 was considered statistically significant.
3. Results A total of 625 elderly subjects, comprised of 394 (63%) women and 231 (37%) men, were enrolled in this study. The mean age of the study population was 72.4 5.6 years (range 65–93 years). The characteristics of the study population (n = 625) are shown in Table 1. Women had higher incidence rates of obesity, hypertension, low creatinine clearance, whereas there were no differences in the rates of DM, duration of DM and urinary incontinence presence between men and women. Men had a higher numbers of prior genitourinary surgery and urolithiasis than women. The overall prevalence of ASB was 6.2% (39/625) among the elderly (8.9% women and 1.7% men) living in the community. Women had a significantly higher prevalence of ASB than men (P < 0.001). The presence of ASB was not associated with the age, number of prior UTI, history of urolithiasis, urinary incontinence, the number of births in women, and prior genitourinary surgery including prostate surgery and hysterectomy. Similarly, several comorbidities such as DM, obesity, hypertension, and creatinine clearance did not significantly influence the risk of ASB. Multivariate regression analysis revealed that female gender increased the prevalence of ASB as an independent correlate (OR: 8.114; 95% CI: 2.015–32.666; P = 0.003). The results of the multiple logistic regression analysis of the possible correlates for the ASB are summarized in Table 2. There were no statistically significant differences between the serum levels of leukocyte counts, erythrocyte sedimentation rate, CRP, HbA1c levels of the elderly subjects with and without ASB.
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Table 1 Clinical characteristics of the study population. Characteristics
Total
Women
Men
P value
Number of patients (n/%) Age in years, mean SD BMI in kg/m2, mean SD Creatinine clearance (ml/h) Hypertension (n/%) SBP (mmHg), mean SD DKB (mmHg), mean SD Duration of hypertension (y) Diabetes mellitus (n/%) Duration of diabetes (y) Obesity (n/%) History of UTI (n/%) History of GUS (n/%) Urinary incontinence (n/%) Urolithiasis (n/%)
625 (100) 72.4 5.6 28.9 5.2 61.3 18.8 420 (67.2) 139.1 18.7 82.2 9.3 12.7 4.0 176 (28.2) 7.2 2.8 238 (39.3) 178 (28.5) 38 (6.1) 176 (28.2) 108 (17.3)
394 (63) 72.1 5.5 30.4 5.3 53.9 15.1 297 (75.4) 138.5 18.5 81.9 9.2 12.5 3.9 104 (26.4) 7.3 2.7 197 (51.7) 140 (35.5) 7 (1.8) 119 (30.2) 55 (14)
231 (37) 72.9 5.8 26.6 3.9 73.8 17.9 123 (53.2) 140.4 19 82.9 9.4 13.2 4.1 72 (31.2) 7.1 2.9 41 (18.3) 38 (16.5) 31 (13.5) 57 (24.7) 53 (22.9)
0.350 < 0.001 < 0.001 < 0.001 0.348 0.291 0.094 0.200 0.314 < 0.001 < 0.001 < 0.001 0.138 0.004
Geriatric assessment tests MMSE, mean SD ADL, mean SD IADL, mean SD S-MNA, mean SD
24.9 1.3 0.7 0.9 12.2 1.3 12.1 0.4
24.8 1.2 0.7 0.9 12.2 1.2 12.1 0.3
25.0 1.4 0.8 1.0 12.2 1.5 12.2 0.4
0.097 0.159 0.858 0.271
SD: standard deviation; BMI: body mass index; UTI: urinary tract infection; GUS: genitourinary surgery; MMSE: the minimental state examination; ADL: the activities of daily living; IADL: the instrumental activities of daily living; S-MNA: the short version of mini nutritional assessment test.
Table 2 The results of the multiple logistic regression analysis of the possible correlates for asymptomatic bacteriuria (ASB). Odds ratio
Gender (female) Age Diabetes mellitus Hypertension Obesity Urinary incontinence Prior GUS Prior UTI Urolithiasis
8.11 0.74 0.82 0.77 1.24 0.60 2.98 0.55 0.30
95% CI
P value
Lower
Upper
2.01 0.34 0.35 0.34 0.55 0.28 0.56 0.23 0.06
32.6 1.59 1.89 1.75 2.79 1.27 15.74 1.28 1.35
0.003 0.442 0.646 0.546 0.597 0.188 0.198 0.554 0.118
ASB: asymptomatic bacteriuria; GUS: genitourinary surgery; UTI: urinary tract infection.
Laboratory values and the risk factors in subjects with and without ASB are presented in Table 3. In addition, the subjects with ASB showed significantly higher rates of pyuria (87.4%) and positive LE and nitrite tests. (P < 0.001) The sensitivity of urine dipstick test for LE and nitrites was 58.1% and 37.2%, respectively, while the specificity for LE and nitrite was higher in the subjects with ASB (82.5%, 99.5%, respectively). Furthermore, the combination of measurements for LE and nitrite in the subjects with ASB was characterized by decreasing sensitivity (20.9%) and increasing specificity (99.6%). Whereas PPV of urine dipstick test for LE, nitrite and the combination of LE and nitrite were 20.7%, 84.2%, 81.8%, respectively, NPV was higher than PPV for LE, nitrite and the combination of LE and nitrite in the subjects with ASB (96.2%, 95.3%, 94.1%, respectively). The most common microorganism isolated was Escherichia coli (E. coli) (66.7%, 26/39), followed by Beta hemolytic streptococci
Table 3 Clinical characteristics and laboratory results of the subjects with and without asymptomatic bacteriuria (ASB). Characteristics and values
Asymptomatic bacteriuria (n = 39)
No bacteriuria (n = 586)
P value
Age in years, mean SD BMI in kg/m2, mean SD Obesity (n/%) Hypertension (n/%) SBP (mmHg), mean SD DKB (mmHg), mean SD Duration of hypertension (y) Diabetes mellitus (n/%) Duration of diabetes (y) Glucose (mg/dL), median Creatinine (mg/dL), median Creatinine clearance (mL/h), median HbA1c (%), median Leukocyte counts (10/uL), median Sedimentation rate (mm/h), median CRP (mg/dL), median History of UTI (n/%) History of GUS (n/%) Urinary incontinence (n/%) Urolithiasis (n/%)
72.2 6.4 29.2 5.1 17 (43.6) 28 (71.8) 140.7 18.0 82.8 10.6 12.2 4.1 9 (23.1) 7.2 2.9 102 1.0 53.5 7.5 7.2 20 0.330 9 (23.1) 2 (5.1) 15 (38.5) 3 (7.7)
72.4 5.5 28.9 5.2 221 (37.7) 392 (66.9) 138.9 18.7 82.1 9.2 12.7 4.0 167 (28.5) 7.1 2.8 104 0.9 57.5 7.0 7.1 18 0.333 169 (28.8) 36 (6.2) 161 (27.5) 105 (17.7)
0.810 0.728 0.482 0.528 0.632 0.682 0.468 0.466 0.386 0.742 0.081 0.147 0.426 0.191 0.306 0.258 0.440 0.795 0.140 0.102
BMI: body mass index; SBP: systolic blood pressure; DBP: diastolic blood pressure; HbA1c: hemoglobin A1c; CRP: c reactive protein; UTI: urinary tract infection; GUS: genitourinary surgery.
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Table 4 Resistance patterns of isolated bacteria in subjects with asymptomatic bacteriuria (ASB). Microorganisms (n)
E. coli (29) Streptococci spp. (6) CNS (2) Klebsiella spp. (1) Enterobacter spp. (1)
Antimicrobial agents (resistance %) Am
Ams
Cf
Sxt
Cip
Tbr
Gm
Amk
Nf
Cro
Tzp
Ipm
Vm
34.3 0 50 0 100
12.5 0 0 0 0
16.1 0 0 0 0
21.2 100 0 0 0
28 0 0 0 0
4 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
0 0 0 0 0
CNS: Coagulase-negative staphylococci; Am: ampicillin; Ams: ampicillin/sulbactam; Cip: ciprofloxacin; Gm: gentamicin; Sxt: trimethoprim/sulfamethoxazole; Amk: amikacin; Nf: nitrofurantoin; Cro: ceftriaxone; Tzp: piperacillin/tazobactam; Ipm: imipenem; Vm: vancomycin.
(10.3%, 4/39), Hemolytic E. coli (7.7%, 3/39), Alpha-hemolytic streptococci (5.1%, 2/39), Coagulase-negative staphylococci (5.1%, 2/39), Klebsiella pneumoniae (2.6%, 1/39) and Enterobacter species (2.6%, 1/39). Rates of resistance in the elderly subjects with ASB were 34.3% for ampicillin, 28% for ciprofloxacin, 21.2% for trimethoprim/sulfamethoxazole (TMX-SMP), and 16.1% for cephalotin. Resistance was lower for some other agents, including 12.5% for ampicillin/sulbactam, and 4% for tobramycin. Multiresistance was detected in 27.6% of E. coli. All the strains were susceptible to nitrofurantoin and parenteral agent including amikacin, gentamicin, ceftriaxon, piperacillin/tazobactam, imipenem and vancomycin (Table 4). 4. Discussion The prevalence of ASB varies among different older persons. Institutionalized older persons have been reported to have a higher prevalence of ASB relative to elderly living in the community [19]. Bacteriuria occurs 8% to 10% in women and 4% to 7% in men older than 70 years among the ambulatory elderly [20]. The present study showed a prevalence of 6.2% for ASB. In addition, ASB was more common in the elderly women than in the elderly men (8.9% vs. 1.7%). All the subjects could be characterized as active, functionally independent, cognitively intact and nutritionally normal elderly residents in the community. Therefore, our data may not be representative of all older persons, especially with functional limitation, cognitive impairment and malnutrition. Studies have evaluated factors predisposing to ASB such as female gender, older age, and the presence of DM. In women, short distal urethra and loss of the estrogen effect after menopause in genitourinary mucosa may promote bacteriuria through increased bacterial colonization or other mechanisms. Chronic comorbid diseases occurring with high frequency in older persons, particularly the in the institutionalized population, are the major contributing factors to bacteriuria [6,8]. When the general population is in concern, a marked and constant increase in the prevalence of ASB with age is documented [3]. However, when limited age range is taken into account, as it is the case in our study, age itself is not a risk factor in the geriatric age range. In the present study, no associations were also found between ASB and BMI, previous history of UTI, genitourinary surgery, urolithiasis, urinary incontinence, DM, obesity and hypertension. In the whole study population, the only consistent risk factor for the presence of ASB was female gender. Recent studies have reported that bacteriuria is associated with hypertension, decreased renal function, and DM [10,21,22]. However, ASB in the absence of urinary obstruction does not lead to impaired renal function and hypertension [23]. In addition, poor glycaemic control and its indicator increased HbA1 c levels are associated with bacteriuria. However, there are also controversial and conflicting issues regarding the relationship between the development of bacteriuria and current glucose values and high
HbA1c. On the other hand, long-standing DM and its micro and macrovascular complications are more important in increased bacteriuria risk and high prevalence [8,24]. In the present study, the older persons had relatively short duration of DM, (mean 7.2 2.8 years) improved glycaemic control, well controlled hypertension (mean 139.1 18.7 to 82.2 9.3 mmHg) and no urinary obstruction. Several studies indicate that ASB is associated with low grade inflammatory activity, which is evidence of a host immune response including elevated cytokines (interleukin1-a, interleukin 6, Tumor necrosis factor-a). They are likely to be found in lower levels in the subjects with ASB than those with UTI [25,26]. On the other hand, detection of cytokine levels is not a practical and a routinely available test. Thus, it is difficult and complex to detect the levels of cytokines in both urine and plasma. In the present study, erythrocyte sedimentation rate, leukocyte count and CRP level, which can be used frequently in daily practice, were evaluated. However, there were no significant differences between elderly with and without ASB. Older persons with ASB may have a host response, but it cannot be detected using the routine conventional methods. Furthermore, the bacteria in ASB may be less virulent, which can lead to a mild immune response or host response might be variable and intermittent. In our study, E. coli was the most commonly isolated microorganism in both sexes. Most of the elderly subjects with ASB have pyuria. Pyuria is inflammation within the genitourinary tract, and it is usually associated with significant bacteriuria [10]. Urinary dipstick test is simple, cheap for a rapid diagnosis of bacteriuria, whereas making a culture is costly and takes at least 24 hours. Most studies have reported that neither pyuria nor dipstick test can be useful in differentiation of ASB and UTI [11,27]. Our results indicate that the subjects with ASB showed high rates of pyuria. Nitrite and LE test measurements have high specificity and relatively low sensitivity. Evaluation of those tests as single tests and in combination with LE and nitrite did not increase the sensitivity of dipstick method. In addition, the negative urine dipstick test seems to be useful in older persons to exclude the presence of bacteriuria. These results were in agreement with the results of previous studies [11,28]. Our data also showed a substantial reduction in susceptibility to antibiotics frequently used in the community such as ampicillin, cephalothin, TMX-SMP and fluoroquinolones for E. coli isolates. Because of unnecessary use of antibiotics, antimicrobial resistance rates increase both among older persons living in community and among older nursing home residents [29]. The results of our study support the recommendation that ASB in older persons should not be treated [2]. There were several limitations in this study. Causal relationships between the possible risk factors and ASB were unclear due to the use of a cross-sectional design. Further longitudinalstudies with follow-up data would give more information about relationship between the possible risk factors and ASB. Another limitation of the study is the relatively small sample size (n = 4) with regard
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to men to make any statistical calculations of some associations between ASB and its related factors; thus, some of our findings require further confirmation. 5. Conclusion ASB is common among the ambulatory older persons, especially in women. In routine practice, the negative urine dispstick test for LE and nitrites seems to be useful in older persons to rule out the presence of bacteriuria. On the other hand, standard laboratory parameters such as erythrocyte sedimentation rate, CRP level, leukocyte counts are not guiding in elderly with ASB. A substantial reduction in susceptibility to antibiotics frequently used in the community such as ampicillin, cephalotin, TMX-SMP, and ciprofloxacin was observed. Therefore, excessive and inappropriate empirical choice of antibiotics may promote the appearance of antimicrobial resistance in older persons living in the community. Thus, antibiotics should not be given routinely in elderly subjects with ASB. When antibiotics are prescribed increasing rates of antibiotics resistance should be considered. Disclosure of interest The authors declare that they have no conflicts of interest concerning this article. References [1] Lin YT, Chen LK, Lin MH, Hwang SJ. Asymptomatic bacteriuria among the institutionalized elderly. J Chin Med Assoc 2006;69:213–7. [2] Nicolle LE, Bradley S, Colgan R, Rice JC, Schaeffer A, Hooton TM. Infectious diseases society of America guidelines for the diagnosis and treatment of asymptomatic bacteriuria in adults. Clin Infect Dis 2005;40:643–54. [3] Juthani-Mehta M. Asymptomatic bacteriuria and urinary tract infection in older adults. Clin Geriatr Med 2007;23:585–94. [4] Zhanel GG, Harding GK, Guay DR. Asymptomatic bacteriuria. Which patients should be treated? Arch Intern Med 1990;150:1389–96. [5] Nicolle LE. Urinary tract infections in the elderly. Clin Geriatr Med 2009;25:423–36. [6] Nicole LE. Asymptomatic bacteriuria in the elderly. Infect Dis Clin North Am 1997;11:647–62. [7] Nicolle LE, Bjornson J, Harding GK, MacDonell JA. Bacteriuria in elderly institutionalized men. N Engl J Med 1983;309:1420–5. [8] Matteucci E, Troilo A, Leonetti P, Giampietro O. Significant bacteriuria in outpatient diabetic and non-diabetic persons. Diabet Med 2007;24:1455–9.
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