Urinary antibody level and survival in bacteriuric institutionalized older subjects.

OBJECTIVE: In a previous study, elevated urine antibody levels in institutionalized subjects with asymptomatic bacteriuria were associated with decreased survival. This study was undertaken to confirm the previous observation in a prospective study in a larger cohort and to explore selected other variables that may be associated with survival. DESIGN: A prospective, 24-month, observational cohort study. SETTING: Three large nursing homes in Winnipeg, Manitoba. PARTICIPANTS: Permanent residents were identified by initial screening urine cultures and subjects with bacteriuria were enrolled. The median age of subjects was 76 years, 51% were women, and the median duration of residence before enrollment was 26 months. Subjects were highly functionally impaired. MEASUREMENTS: Monthly urine specimens were collected for culture, leukocyte count, and urine antibody. Serum specimens for antibody to uropathogens and IL6 were obtained at enrollment and every 6 months. Anthroporphometric tests of nutritional status and functional and mental status were also measured every 6 months. Residents were stratified as having elevated or not elevated urine antibody, based on the initial urine specimen. The mean urine antibody for all of each subject's specimens was also calculated, and subjects were stratified as low, intermediate, or elevated urine antibody. Outcomes measured included mortality, infection and antibiotic use, and functional, mental, and nutritional decline. RESULTS: Ninety-eight bacteriuric subjects were enrolled in the study; 34 (35%) had elevated urine antibody and 64 (65%) had not elevated urine antibody. The two groups did not differ in demographic features, co-morbidities, functional status, medication use, or infecting organisms. Survival was significantly (P < .001) poorer in the group with elevated urine antibody. At 24 months, 35% of subjects with an elevated urine antibody were alive compared with 75% with a low urine antibody level. This survival difference was consistent when the two groups were stratified by sex, institution, and presence of a chronic indwelling catheter. Subjects with elevated urine antibody had no evidence for accelerated functional or nutritional decline during the study period compared with the group with low urine antibody. These subjects did, however, have an increased incidence of episodes of symptomatic urinary infection and infections at non-urinary sites. CONCLUSIONS: Older, bacteriuric, institutionalized subjects with elevated urine antibody had decreased survival rates compared with subjects with lower urine antibody levels. There is no clinical evidence to support accelerated decline caused by chronic infection to explain this observation. Urine antibody may be a marker for immune dysregulation, which precedes death in older impaired subjects.

Serological study of responses to selected pathogens causing respiratory tract infection in the institutionalized elderly.

In a prospective 2-year study, serological responses to selected pathogens were analyzed in 224 episodes of fever attributable to respiratory tract infection (51.8%) or of unknown source (48.2%) in 131 residents of two long-term-care facilities. A serological response was identified in 45 episodes (20.1%): Chlamydia pneumoniae (14 episodes), Haemophilus influenzae type b (1), influenza virus type A (14), respiratory syncytial virus (RSV;2), parainfluenza virus type 3 (7), C. pneumoniae and H. influenzae (3), C. pneumoniae and influenza virus type A (2), C. pneumoniae and RSV (1), and C. pneumoniae and parainfluenza virus type 3 (1). No serological responses to Chlamydia psittaci, Chlamydia trachomatis, parainfluenza virus types 1 and 2, influenza virus type B, or Mycoplasma pneumoniae were seen. Vaccination did not affect the duration of fever in those residents with serologically confirmed influenza A. Serologically confirmed C. pneumoniae infection was detected in 9.4% of all febrile episodes. Serological responses to a second agent were detected in 33% of the patients with C. pneumoniae infections, and these dual infections were associated with an underlying malignancy (P = .02). C. pneumoniae should be recognized as a potential pathogen when choosing empirical antimicrobial therapy for respiratory tract infection in residents of long-term-care facilities.

Febrile urinary infection in the institutionalized elderly.

PURPOSE: Bacteriuria is common among institutionalized elderly populations, but the contribution of urinary infection to febrile morbidity is unknown because of difficulties in clinical ascertainment. This study was undertaken to febrile morbidity using both clinical and serologic criteria. METHODS: Episodes of fever in residents of two long-term care institutions were identified prospectively for 2 years. Serum and urine specimens were obtained initially and at 4 weeks. The proportion of episodes attributable to urinary infection was determined by both standard clinical criteria proposed for use in these populations and serum antibody response to uropathogens. RESULTS: For 372 fewer episodes, 211 met clinical criteria for infection: 147 (40%) of the respiratory tract; 26 (7%) of the genitourinary tract; 25 (6%) of the gastrointestinal tract; and 13 (3%) of skin and soft tissue. Of the remaining 161 fever episodes, 2 (1%) were noninfectious and 159 (43%) were of unknown origin. The prevalence of bacteriuria for residents with nongenitourinary sources of fever varied from 32% to 75%. An antibody response meeting serologic criteria for urinary infection occurred in 26 (8.3%) of 314 episodes with paired sera obtained; 10 (43%) of 23 identified clinically as genitourinary infection, 14 (11%) of 132 unknown, 1 (4%) of 25 gastrointestinal, and 1 (0.8%) of 122 respiratory. The positive predictive value of bacteriuria for febrile urinary infection identified by clinical criteria was was 11% (95% confidence interval [CI] 4%, 18%) and identified by serologic criteria was 12% (95% CI 7%, 17%). CONCLUSIONS: Urinary infection contributes to less than 10% of episodes of clinically significant fever in this high-prevalence bacteriuric population. A restrictive clinical definition for genitourinary infection has poor sensitivity and specificity compared with serologic criteria for identification of fever of urinary source, and bacteriuria has a low predictive value for identifying febrile urinary infection.

Prospective study of decubitus ulcers in two long term care facilities.

The incidence and prevalence of decubitus ulcers, and their complications and microbiology were studied prospectively in two large long term care facilities in Winnipeg, Manitoba between January 1, 1989 and December 30, 1990. The initial prevalence of decubitus ulcers was 2.6 and 1.6% at the two institutions, with an incidence of 3.4 and 4.8 per 100,000 resident days, respectively. The incidence of decubitus ulcer infection was 1.4 per 1000 ulcer days. The only other complication identified was in one resident who required an indwelling catheter to permit ulcer healing. An average of 2.4 organisms grew from surface swabs of ulcers; anaerobes were isolated from 14% of cultures. Aspirates from clinically noninfected ulcers had bacteria isolated in 30% of specimens. Two-thirds of organisms isolated were considered potentially pathogenic. Concurrent bacteriuria was present for 75% of sampling episodes. Organisms present in the urine were simultaneously isolated from decubiti in only 5% of specimens. Decubitus ulcers are uncommon in long term care institutions. The urinary tract of the bacteriuric elderly appears to be an infrequent source of organisms colonizing decubiti.

Gross hematuria in residents of long-term-care facilities.

PURPOSE: To describe the epidemiology and characteristics of gross hematuria in elderly residents of nursing homes and to identify the associations of gross hematuria with urinary infection and the potential contribution of urinary infection to morbidity. PATIENTS AND METHODS: This was a prospective, descriptive study of episodes of gross hematuria identified by the nursing staffs at two long-term-care facilities over 2 years. Episodes were characterized with respect to patient variables, presence of bacteriuria, duration of hematuria, therapeutic interventions, and genitourinary investigations. Clinical and serologic criteria were used to identify invasive infection. RESULTS: The incidence of gross hematuria was 31/100,000 resident days. Bacteriuria was present in 58 (74%) of 78 episodes with evaluable cultures. Fifty-two (61%) episodes lasted more than 24 hours, 25 (29%) were temporally associated with fever, and antimicrobials were given for 53 (61%) episodes. Gross hematuria occurred more frequently in men than in women and was more frequently associated with fever in men. Twenty-four (28%) episodes occurred in subjects with indwelling catheters, 30 (34%) in subjects with known genitourinary abnormalities, 26 (30%) in subjects with no genitourinary investigations, and 4 (4.6%) in subjects with genitourinary investigations but no abnormalities identified. No adverse clinical outcomes were identified in patients in whom antimicrobial therapy was not initiated. The maximal estimated incidence of invasive urinary infection associated with hematuria was 5.8/100,000 resident days, and of bacterial hemorrhagic cystitis, 6.3/100,000 resident days. CONCLUSIONS: These data suggest that underlying genitourinary abnormalities are present in most elderly institutionalized subjects with gross hematuria when genitourinary investigations are performed. Although bacteriuria is usually present, urinary infection, by itself, is an infrequent cause of gross hematuria. Afebrile hematuria without irritative symptoms probably does not require antimicrobial therapy. A standard approach to this clinical problem in the institutionalized elderly should be developed to optimize patient management and appropriate use of antimicrobial therapy.

Urinary immunoreactive interleukin-1 alpha and interleukin-6 in bacteriuric institutionalized elderly subjects.

Urinary immunoreactive interleukin-1 alpha and interleukin-6 levels were measured in specimens obtained from elderly institutionalized subjects, including 67 asymptomatic subjects (51 of whom were bacteriuric), 34 with fever from nonurinary sources, 15 with bacteriuria and 9 with symptomatic urinary infection. For bacteriuric subjects urinary interleukin-1 alpha and interleukin-6 levels were measurable in 18 (35%) and 22 (43%) asymptomatic subjects, respectively, 9 (60%) and 8 (53%) with nonurinary sources of fever, respectively, and 6 (67%) and 7 (78%) with urinary infection, respectively. For subjects without bacteriuria 1 of 16 (6.3%) who were asymptomatic and 5 (25%) with nonurinary sources of fever had measurable urinary interleukin-1 alpha, and 2 (13%) and 1 (5.3%), respectively, had measurable interleukin-6. Presence of interleukin-1 alpha or interleukin-6 was significantly associated with bacteriuria for asymptomatic and symptomatic subjects. Interleukin-1 alpha or interleukin-6 quantitative levels were lower in subjects without than with bacteriuria. Quantitative levels of interleukin-6 tended to decrease for bacteriuric subjects with symptomatic infection between acute and convalescent specimens. These observations suggest that interleukin-1 alpha and interleukin-6 are produced in association with bacteriuria in some elderly subjects. Variation in local cytokine production with time and the clinical significance of these observations require further study.

Asymptomatic bacteriuria, urinary antibody, and survival in the institutionalized elderly.

OBJECTIVE: To compare clinical status of elderly institutionalized subjects with asymptomatic bacteriuria and normal urinary antibody to those with elevated urinary antibody to the major outer membrane of Escherichia coli. DESIGN: Retrospective review. SETTING: Long term facility for the elderly. PARTICIPANTS: Convenience sample of 63 elderly subjects, 26% of those resident in the institution, aged 78.8 +/- 8.4 years with urine specimens collected and stored in 1987. MAIN OUTCOME MEASURES: Differences in clinical or functional status, demographic features, and outcome during 3-years follow-up between bacteriuric subjects with normal and elevated urine antibody. RESULTS: Thirteen subjects had no bacteriuria, and 12 had infrequent, intermittent bacteriuria; 38 (60%) had persistent bacteriuria, including four with frequent, intermittent infections. In the persistently bacteriuric group, 18 (47%) had persistently elevated urine antibody. There was no significant differences between bacteriuric residents with normal vs elevated urine antibody in clinical or functional status, age, duration of residence, or infecting organisms. However, 11 of 20 in the cohort with normal urine antibody were alive at 3 years compared to 3 of 18 with elevated urine antibody (P = 0.014). CONCLUSIONS: Elderly institutionalized subjects with persistent bacteriuria and elevated urine antibody have decreased survival compared to those with normal urine antibody. No differences in underlying illness or clinical course to explain this survival difference were identified.

Prevalence of antibody to hepatitis C virus in an isolated Canadian Inuit settlement.

Sera from 720 inhabitants of Baker Lake, Northwest Territories, a community with high rates of hepatitis A and B infection, were tested for antibody to hepatitis C virus by commercial enzyme-linked immunosorbent assay. Only two individuals (0.3%) were positive, a 63-year-old female and an unrelated 10-year-old male. Neither individual was at increased risk of hepatitis C virus exposure. The results of this study indicate that hepatitis C virus infection is no more common in this northern Canadian Inuit settlement than it is in the blood donor population of southern Canada.

Urinary IgG and IgA antibodies in elderly individuals with bacteriuria.

We studied the urinary IgG and IgA antibody in elderly subjects without bacteriuria, with asymptomatic bacteriuria and symptomatic urinary infection. Elderly individuals with asymptomatic bacteriuria had significantly elevated antibody levels relative to controls. When followed up to 12 months with persistent bacteriuria, antibody levels tended to persist but were variable. In elderly women with elevated urinary antibody titers, site of infection tended to be localized to the kidney, but antibody levels within the control range occurred as frequently as elevated antibody levels for renal infection. Subjects with invasive urinary infection had significantly elevated antibody levels at onset of symptoms, with levels increased or decreased when repeated 2-4 weeks later. Further studies to clarify the clinical significance of these observations are necessary.

Antibodies to major outer membrane proteins of Escherichia coli in urinary infection in the elderly.

The serologic response to infection in elderly bacteriuric subjects and young women with acute pyelonephritis was measured with an enzyme-linked immunosorbent assay (ELISA) using the major outer membrane protein complex (MOMP) of one Escherichia coli strain as antigen. Elderly controls and subjects with asymptomatic bacteriuria had variable titers; control titers were significantly lower than those with asymptomatic bacteriuria. Titers were stable over 2-12 w in asymptomatic subjects. Elderly subjects with invasive infection and women with pyelonephritis demonstrated increases in titer between acute and convalescent serum for E. coli and other Enterobacteriaceae. With a convalescent specimen with an antibody titer greater than or equal to 3 standard deviations (SD) above the acute, the sensitivity of the MOMP ELISA for identifying invasive infection was 74%, the specificity 86%, the positive predictive value 82%, and the negative predictive value 79%. With the criteria of greater than or equal to 3 SD or an initial serum to control ratio of greater than or equal to 15 these parameters were 95%, 82%, 82%, and 95%, respectively. These initial investigations suggest the MOMP of E. coli may be an antigen with wide cross-reactivity, suitable for use as an objective test to identify invasive Enterobacteriaceae urinary infection.

Immunoblot analysis of serologic response to outer membrane proteins of Escherichia coli in elderly individuals with urinary tract infections.

We used immunoblotting to examine the serologic antibody responses to outer membrane proteins (OMP) of Escherichia coli in both symptomatic and asymptomatic elderly subjects with urinary tract infections. Controls with no present or past urinary tract infections showed variable weak immunoglobulin G (IgG) antibodies to OMP of infecting strains. Elderly individuals with asymptomatic infections demonstrated antibody to both lipopolysaccharide (LPS) and OMP of their infecting strain, with consistent cross-reactivity to OMP of other infecting strains. Young females with acute pyelonephritis showed an IgG response to LPS and OMP with cross-reactivity to OMP of other strains. Elderly individuals with symptomatic invasive infections had strong reactions to both LPS and OMP in specimens collected during the acute phase, generally with an increase in intensity in specimens from convalescent patients. They also demonstrated extensive cross-reactivity to LPS and OMP from all other infecting strains. IgM antibody was not observed in any patients. These data confirm other reports of low levels of antibodies to OMP of E. coli in normal populations. Asymptomatic bacteriuria in this population is associated with antibody responses to the LPS and OMP of the infecting strain. Elderly individuals with invasive infections had initial reactions to the infecting strain with an apparent increase in intensity during convalescence. Antibodies to the major OMP appear to be broadly cross-reactive.

Serum modulation of insulin action: effects on rat gingival fibroblast metabolism.

Serum is reported to reduce the sensitivity of cells in culture to insulin. The effect of serum concentration in the growth medium on the responsiveness of control (C) and streptozotocin diabetic (D) rat gingival fibroblasts to insulin was measured by monitoring cellular DNA, RNA, total protein and medium hydroxyproline (collagen) levels, as well as the cellular uptake of C14-alpha-NH2-isobutyrate (alpha-AIB) and H3-2-deoxyglucose (2DG). The cells were grown in alpha-MEM at 5, 10, 15 or 20% FCS with 0, 10(-12), 10(-10), 10(-8) and 10(-6) M insulin used at each serum level. Insulin effects in the absence of serum were not assessed. For both the C and D rat cells, the DNA increased proportionately with increasing serum and insulin levels. In contrast, RNA and total cell protein increased with increase in insulin and decrease in serum, the magnitude of the effect being greater in C than in D cells. The insulin stimulation of both 2DG and alpha-AIB uptake and of collagen secretion varied inversely with serum concentrations. The magnitude of the insulin-serum interaction on metabolite uptake was greater for the D rat cells. These data indicate that serum significantly reduced the cell response to insulin stimulated metabolite uptake and collagen secretion, but was without apparent effect on the intracellular insulin responsive parameters. They suggest that serum factor(s) interfere with the availability of insulin to the cell and that the D rat cells are most affected.