ORIGINAL STUDIES Asymptomatic Bacteriuria in Institutionalized Elders in Israel Raul Raz, MD, Diana Gronich, BS.c, Yoshua Ben-Israel, MD, and Lindsey E. Nicolle, MD Objectives: To document the prevalence of asymptomatic bacteriuria in patients in one large long-term care facility, and describe clinical outcomes in initially bacteriuric and nonbacteriuric residents during prospective observation encompassing one year. Methods: Patients enrolled in the study were residents of the Haim-Shoham Geriatric Center, a longterm care institute with 800 inhabitants. Twenty patients were related randomly for study enrollment on each of the ten wards. A urine culture was obtained from the enrolled patients. A second culture was obtained within one week if the initial culture grew Ն 105 colony-forming units per milliliter (cfu/ml) of at least one uropathogen. Demographic data and comorbidities, as well as most recent laboratory results, were recorded for all patients enrolled. Subjects were followed prospectively for one year or until death. Clinical events and usage of antibiotics were recorded. In patients with asymptomatic bacteriuria, repeated urine cultures were obtained every two months. Results: Eighty-five (43.3%) of a total of 196 elder res- There is a high prevalence of bacteriuria among institutionalized older people, with 25–50% of women and 15– 48% of men bacteriuric at any time.1 Bacteriuria is usually asymptomatic,2 and the impact of asymptomatic bacteriuria on patient outcomes has been controversial. Prospective studies have reported similar survival between bacteriuric and nonbacteriuric institutionalized subjects, although the bacteriuric group is consistently more functionally impaired.3,4 Where increased mortality has been observed in bacteriuric subjects, the association with bacteriuria has disappeared following adjustment for covariates.5 Infectious Diseases Unit, Haemek Medical Center, Afula, and the Technion, Faculty of Medicine, Haifa (R.R.); Haim Shoham Geriatrics Institute, Pardes Hana (D.G. and Y.B.I.), Israel; and the Department of Internal Medicine, University of Manitoba, Canada (L.E.N.). Address correspondence to: Raul Raz, MD, Director, Infectious Diseases Unit, Haemek Medical Center, Afula, 18101, Israel. Copyright ©2001 American Medical Directors Association ORIGINAL STUDIES idents screened presented asymptomatic bacteriuria. There were no differences between patients with and without asymptomatic bacteriuria in age, gender, and underlying diseases. Patients with asymptomatic bacteriuria were significantly more bed-ridden (91.7% vs. 82.1%, P ϭ 0.05); demented (78.8% vs. 59.8%, P ϭ 0.03); and incontinent of urine (93% vs. 71.4%, P Ͻ 0.0001) and bowel (85.8% vs. 59.3%). During one year of prospective observation, bacteriuric patients had a mortality rate of 25.9%, compared to 7.1% for nonbacteriuric (P Ͻ 0.0001). Mortality in the group with bacteriuria was higher due to both urinary infection and other causes. Conclusions: In our population, asymptomatic bacteriuria was associated with increased functional impairment and increased mortality over 12 months. The increased mortality, however, was not fully attributable to urinary infection. (J Am Med Dir Assoc 2001; 2: 275– 278) Keywords: asymptomatic bacteriuria; bacteriuria in the elderly; asymptomatic bacteriuria and death Prospective, randomized studies have also shown no difference in clinical outcomes, including mortality, with treatment of asymptomatic bacteriuria.5–7 Older residents of longterm care facilities who have long-term indwelling catheters, however, have been reported to have decreased survival rates.8 This finding has been attributed to bacteriuria, but patients with indwelling catheters are medically and functionally different than noncatheterized patients, and bacteriuria, per se, has not been documented to be the direct cause of mortality differences. Several studies have also postulated a relationship between bacteriuria and hypertension or renal failure,9 but none of these associations have been confirmed in prospective studies. This study was undertaken to document the prevalence of asymptomatic bacteriuria in patients in one large long-term care facility, and describe clinical outcomes, including mortality, in initially bacteriuric and nonbacteriuric residents during prospective observation for one year. Raz et al. 275 MATERIAL AND METHODS Institution and Study Design Patients enrolled in the study were residents of the HaimShoham Geriatric Center, a long-term care institute with 800 inhabitants in Pardes Hana, Israel. This institution is funded by the Ministry of Health in Israel, with 90% of the residents Jewish, and the majority from middle or lower economic classes. The residents are highly functionally impaired, with two-thirds being fully bedridden. The study protocol was reviewed and approved by the local Helsinki Committee, and informed consent obtained from each patient or family. There are approximately 40 patients in each ward, and we decided to enroll randomly half from each ward–20 patients per ward (approximately 200 patients). Patients were excluded if they had signs or symptoms suggestive of symptomatic urinary infection, or had taken antibiotics during the last month. A urine culture was obtained from enrolled patients by nurses according to an established protocol for collecting urine. If the initial urine culture had Ն 105 colony-forming units per milliliter (cfu/ml) of at least one organism, a second sample was obtained within one week. Patients with initial negative cultures did not have a repeat specimen obtained. Demographic data and comorbidities, as well as most recent laboratory results, were recorded for patients enrolled. Subjects were followed prospectively for one year, or until death. Clinical events, including episodes of infection, antibiotic use, and death were assessed and recorded at two-month intervals. Patients with asymptomatic bacteriuria at the initial survey had urine specimens for culture repeated at two-month intervals; the nonbacteriuric group did not have subsequent urine specimens obtained. Laboratory Methods Urine specimens were obtained by a clean catch method in noncatheterized subjects. Study subjects with an indwelling urethral catheter had a urine specimen collected immediately following catheter replacement. Urine specimens were transported promptly to the laboratory, and culture was performed using a dipstick method. Bacterial isolates present at Ն105 cfu/ml were identified using standard methods.10 Leukocyte esterase and nitrate tests performed by dipstick were recorded for each of the subsequent specimens collected at two monthly intervals in the bacteriuric group. Definitions and Data Analysis Urinary tract infection was defined microbiologically by growth of Ն105 cfu/ml of one or more organisms. Asymptomatic bacteriuria was identified when two consecutive positive urine cultures with the same microorganism(s) were obtained in a patient free of urinary symptoms such as dysuria, frequency, burning sensation, or loin pain. In patients who were unable to provide an accurate history, asymptomatic bacteriuria was identified by signs of urosepsis, such as fever, chills, leukocytosis, or clinical deterioration. Patients with an initial positive culture and repeat negative culture at initial screening were enrolled as negative for follow-up. Any positive result (ie, 1ϩ or greater) was designated as a positive leuko276 Raz et al. cyte esterase or nitrate test. The diagnosis of urosepsis was made in the presence of one or more clinical signs and symptoms, including fever, chills, hypothermia, or clinical deterioration with no other source of infection, together with leukocytosis or leukopenia, pyuria, and a positive urine culture. Standard parametric and nonparametric tests were used for data analysis. The t test was used for means, the chi-squared test or Fisher’s exact test for nominal values, and the Wilcoxon rank sum test for nonnormally distributed values. Life table analysis used the Kaplan-Meier method with a log rank test of difference. RESULTS One hundred and ninety seven patients were included in the survey; asymptomatic bacteriuria was present at initial screening in 85 (43.1%). Patients with and without asymptomatic bacteriuria were similar in age, gender, residence duration, underlying diseases, and presence or absence of an indwelling catheter (Table 1). However, patients with asymptomatic bacteriuria were more functionally impaired, with a significantly high proportion being bedridden, demented, or experiencing urine and bowel incontinence. Escherichia coli was the most frequent species, isolated in 54 (64%) patients. Other organisms isolated included Klebsiella pneumoniae, 13 (15%); Providencia species (spp.), 9 (7.1%); Proteus mirabilis, 4 (4.7%); and 3 (3.5%) each of Pseudomonas spp., Enterobacter spp., and Enterococcus spp. Staphylococcus epidermidis was present in 8 (8.4%) bacteriuric residents. Ten patients (12%) had polymicrobial bacteriuria. The proportion of initially bacteriuric subjects who remained bacteriuric at the two monthly screening intervals was 100% during twelve months, 85% (63 had a persistent infection and 9 a new uropathogen), 90% (60 and 12), 88% (65 and 8), 86% (60 and 13) and 89% (67 and 9) at the following two-months survey. Eighteen of the 57 patients who survived one year had persistent bacteriuria with the same organism; 14 E coli and two each of Klebsiella spp. and Pseudomonas aeruginosa. For these subsequent urine specimens, the leukocyte esterase test had a sensitivity of 94.5%, specificity of 65.2%, positive predictive value of 95.4%, and a negative predictive value of 61% for bacteriuria. The nitrate test had a sensitivity of 56%, specificity of 97%, positive predictive value of 98%, and negative predictive value of 21%. At one year, 22/85 (25.9%) initially bacteriuric residents had died compared to 8/112 (7.1%) nonbacteriuric (P Ͻ 0.0001); (OR ϭ 4.5,95% CI [1.9, 10.8]) (Table 2). Other characteristics explored in the univariant analysis that showed a trend toward higher mortality included dementia (24/134, 17.9% vs. 6/63, 9.5%; P ϭ 0.1126), being bedridden (26/169, 15.4% vs. 3/27, 11.1%; P ϭ 0.410), and experiencing urine (26/159, 16.4% vs.3/35, 8.6%; P ϭ 0.242) or bowel incontinence (24/146, 16.4% vs. 3/43, 7.0%; P ϭ 0.119). The proportion of antibiotic days were similar for the two groups (P ϭ 0.902). Twelve (14.1%) patients with bacteriuria had 15 episodes of symptomatic urinary infection and 8 (7.1%) of 112 without bacteriuria (P ϭ 0.1) experienced ten episodes. Nine JAMDA – November/December 2001 Table 1. Demographic and Clinical Characteristics of the Patients With and Without Asymptomatic Bacteriuria Asymptomatic bacteriuria Yes )%34( 58 ؍ Mean age (years) Range Male/Female Duration residence (months) Underlying Diseases Diabetes Mellitus IDDM IHD CVA COPD Malignancies Mobility Partially mobile Bedridden Mental Status Dementia Competent Urine incontinence Bowel incontinence Chronic indwelling catheter Laboratory Hemaglobin White blood cells Serum albumin Serum creatinine 84 Ϯ 7.9 66–99 11 (12.9%)/74 (87.1%) 19.3 Ϯ 5.2 P value No )%1.75( 211 ؍ 83.4 Ϯ 9.1 63–92 18 (16.0%)/94 (83.9%) 21.1 Ϯ 6.4 N.S. 29 (34.1%) 5 43 (50.5%) 32 (37.6%) 3 (3.5%) 7 (8.2%) 43 (38.3%) 3 59 (52.6%) 44 (39.2%) 5 (4.4%) 10 (8.9%) N.S. 7 (8.2%) 78 (91.7%) 20 (17.9%) 92 (82.1%) P ϭ 0.05 67 (78.8%) 18 (21.1%) 79 (93%) 73 (85.8%) 15 (17.6%) 67 (59.8%) 45 (40.2%) 80 (71.4%) 73 (65.2%) 17 (15.1%) P Ͻ 0.003 12.6 Ϯ 1.8 (8–14.8) 6.8 Ϯ 2.2 (4.0–12.8) 3.8 Ϯ 0.4 (2.4–4.8) 0.8 Ϯ 0.6 (0.3–3.0) N.S. 12.1 Ϯ 1.5 (7.6–15.7) 7.1 Ϯ 2.1 (3.5–13.8) 3.9 Ϯ 0.6 (2.6–5.4) 0.9 Ϯ 0.3 (0.1–2.4) N.S. N.S. P Ͻ 0.0001 P Ͻ 0.0001 N.S. IDDM ϭ insulin dependent diabetes mellitus; IHD ϭ ischemic heart disease; CVA ϭ cerebrovascular accident; COPD ϭ chronic obstructive lung disease; N.S. ϭ not significant. (41%) of 22 bacteriuric subjects died because of urosepsis, and two (25%) of 8 without bacteriuria (Fisher’s exact test ϭ 0.470). The bacteriuric group also had increased mortality from other causes, particularly cerebrovascular accidents and myocardial infarction (Table 2), but we did not find significant statistical differences. Figure 1 displays the differences in the proportion of survival rates between the residents with and without asymptomatic bacteriuria during the 12 months’ follow-up. DISCUSSION Table 2. Outcome in Residents With and Without Asymptomatic Bacteriuria Bacteriuria All subjects P value Yes (N )58 ؍ Infections: Symptomatic UTI Upper respiratory Pneumonia Cellulitis Decubitus ulcer Fever, site unknown Chronic osteomyelitis Antibiotic courses Days (%) Deaths Symptomatic UTI Pneumonia CVA/MI No (N )211 ؍ 95 15* 21 12 12 8 24 3 92 111 (10) 22 (25.9%) 9 3 10 90 10† 26 13 9 5 26 1 90 104 (6.4) 8 (7.1%) 2 3 3 0.1 0.9 Ͻ0.0001 0.4 CVA ϭ cerebrovascular accident/MI ϭ myocardial infarction; UTI ϭ urinary tract infection. *4 with bacteremia. † 2 with bacteremia. ORIGINAL STUDIES The prevalence of bacteriuria in this long-term care facility is similar to previous studies from other facilities that provide Fig. 1. Life table analysis of long-term care residents initially identified as bacteriuric or nonbacteriuric. Raz et al. 277 care to a highly functionally impaired older population.1 Our observation of a significantly higher occurrence of bacteriuria in patients with greater functional impairment, and the distribution of infecting organisms observed are also consistent with other reports.1 There are, however, some unique aspects of this study population. A much higher proportion was bedridden than in previous reports, suggesting a greater degree of functional impairment. In addition, urosepsis and bacteremia were identified more frequently than in other populations.6,7,10 Death from urosepsis is infrequent in other reports,11,12 but was responsible for 37% of deaths in this population. We observed an increased mortality during one-year follow-up in those identified as bacteriuric at initial screening, compared to those who were not bacteriuric. This observation is consistent with other studies that have reported decreased survival in the bacteriuric institutionalized elder population.5,13 The bacteriuric and nonbacteriuric populations were not similar in baseline characteristics, and the more functionally impaired bacteriuric subjects may be anticipated to have decreased survival. A trend toward increased mortality with increasing functional impairment was observed, and this is consistent with other studies where the increased mortality associated with bacteriuria did not persist when corrected for covariates.5 Bacteriuric residents also had an increased frequency of death from causes other than urosepsis, such as myocardial infarction and cerebrovascular accident. In addition, although numbers are small, the proportions of bacteriuric and nonbacteriuric patients who experienced urosepsis and died from urosepsis, were not significantly different. This suggests bacteriuria is a marker for a more impaired population, rather than a direct cause of increased mortality. Even if mortality is directly attributable to asymptomatic urinary infection, current evidence does not suggest antimicrobial treatment of bacteriuria can modify this outcome. Older institutionalized populations have a high recurrence rate of urinary infection following antimicrobial therapy.5,7 Consequently, it is not realistic to expect that these individuals can be maintained free of bacteriuria. Prospective randomized trials of antimicrobial therapy compared with no antimicrobial therapy in long-term care residents with asymptomatic bacteriuria have not shown any benefits in patients treated with antimicrobials.5,7 In fact, there was a trend to increased mortality with antimicrobial therapy for both men6 and women.7 Thus, an observation of increased mortality in bacteriuric subjects 278 Raz et al. should not be interpreted as an argument for treatment of asymptomatic bacteriuria. In our institutionalized population, we observed, as have others, that individuals with a greater level of functional impairment have a greater likelihood of bacteriuria. In addition, a very high prevalence of bacteriuria in the population was confirmed. Our observation of an increased mortality in the group that was initially identified as having asymptomatic bacteriuria requires further exploration14. ACKNOWLEDGMENTS We would like to thank Mrs. Frances Nachmani for her secretarial assistance with this manuscript. REFERENCES 1. Nicolle LE. Urinary tract infections in long-term care facilities. Infect Control Hosp Epidemiol 1993;14:220 –225. 2. Nicolle LE. Asymptomatic bacteriuria in the elderly. Infect Dis Clinics North Am 1997;11:647– 662. 3. Nicolle LE, Henderson E, Bjornson J, et al. The association of bacteriuria with resident characteristics and survival in elderly institutionalized males. Ann Intern Med 1987;106:682– 686. 4. Nicolle LE, Brunka J, McIntyre M, et al. Asymptomatic bacteriuria, urinary antibody, and survival in the institutionalized elderly. J Am Geriatr Soc 1992;40:607– 613. 5. Abruptyn E, Mossey J, Berlin JA, et al. Does asymptomatic bacteriuria predict mortality and does antimicrobial treatment reduce mortality in elderly ambulatory women? Ann Intern Med 1994;120:827– 833. 6. Nicolle LE, Bjornson J, Harding GK, MacDonell JA. 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Twelve month surveillance of infections in institutionalized elderly men. J Am Geriat Soc 1984;32:513–519. 13. Gross JS, Neufeld RR, Libow LS, et al. Autopsy study of the elderly institutionalized patient. Arch Intern Med 1988;148:173–176. 14. Dontas AS, Kasviki-Charvati P, Papanayiotou PC, Marketos SG. Bacteriuria and survival in old age. N Engl J Med 1981;304:939 – 43. JAMDA – November/December 2001