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Clinical Infectious Diseases | 1999

Guidelines for Antimicrobial Treatment of Uncomplicated Acute Bacterial Cystitis and Acute Pyelonephritis in Women

John W. Warren; Elias Abrutyn; J. Richard Hebel; James R. Johnson; Anthony J. Schaeffer; Walter E. Stamm

This is part of the series of practice guidelines commissioned by the Infectious Diseases Society of America (IDSA) through its Practice Guidelines Committee. The purpose of this guideline is to provide assistance to clinicians in the diagnosis and treatment of two specific types of urinary tract infections (UTIs): uncomplicated, acute, symptomatic bacterial cystitis and acute pyelonephritis in women. The guideline does not contain recommendations for asymptomatic bacteriuria, complicated UTIs, Foley catheter-associated infections, UTIs in men or children, or prostatitis. The targeted providers are internists and family practitioners. The targeted groups are immunocompetent women. Criteria are specified for determining whether the inpatient or outpatient setting is appropriate for treatment. Differences from other guidelines written on this topic include use of laboratory criteria for diagnosis and approach to antimicrobial therapy. Panel members represented experts in adult infectious diseases and urology. The guidelines are evidence-based. A standard ranking system is used for the strength of the recommendation and the quality of the evidence cited in the literature reviewed. The document has been subjected to external review by peer reviewers as well as by the Practice Guidelines Committee and was approved by the IDSA Council, the sponsor and supporter of the guideline. The American Urologic Association and the European Society of Clinical Microbiology and Infectious Diseases have endorsed it. An executive summary and tables highlight the major recommendations. Performance measures are described to aid in monitoring compliance with the guideline. The guideline will be listed on the IDSA home page at http://www.idsociety.org It will be evaluated for updating in 2 years.


Annals of Internal Medicine | 1998

Dental and Cardiac Risk Factors for Infective Endocarditis: A Population-Based, Case-Control Study

Brian L. Strom; Elias Abrutyn; Jesse A. Berlin; Judith L. Kinman; Roy S. Feldman; Paul D. Stolley; Matthew E. Levison; Oksana M. Korzeniowski; Donald Kaye

Infective endocarditis is uncommon but potentially fatal. Administration of antibiotic prophylaxis is conventional [1], but data supporting its effectiveness derive solely from anecdotal reports, studies of bacteremia after dental and other procedures, and animal models. The low incidence of disease [2] has made randomized human trials of antibiotic effectiveness impractical. Even if effective, antibiotic prophylaxis should be reserved for patients at increased risk, such as those with cardiac abnormalities who are undergoing dental procedures. However, controlled human studies of risk factors are lacking. Previous case series indicate that approximately 15% of patients with infective endocarditis caused by mouth organisms had undergone a recent dental procedure [3], but the comparable percentage from a general population is unknown. The single hospital-based casecontrol study did not find an elevated risk associated with dental therapy, except for a borderline increase with dental scaling [4]. We are unaware of controlled human studies that quantify the risk for infective endocarditis associated with cardiac valve abnormalities other than mitral valve prolapse. We therefore conducted a population-based casecontrol study to evaluate and quantify risk factors for infective endocarditis, especially those considered by the American Heart Association (AHA) to be indications for antibiotic prophylaxis [1]. Methods Participants From August 1988 to November 1990, we maintained surveillance for infective endocarditis in 54 hospitals of the Delaware Valley Case-Control Network, a population-based network of hospitals in the eight counties that constitute the Philadelphia Metropolitan Statistical Area and the county of New Castle, Delaware. Patients with a putative diagnosis of infective endocarditis were identified by hospital personnel and were reported to study nurses, who also actively sought cases. To assess the completeness of ascertainment, five high-yield hospitals and three low-yield hospitals were asked to list all patients discharged with a diagnosis of endocarditis over 3 months. These lists were compared with those obtained from our surveillance; charts were reviewed when differences were identified. We obtained informed consent from physicians and case-patients, then used structured forms to abstract medical records, including echocardiographic reports and hospital laboratory information on the infecting organism. We deleted information on purported risk factors for infective endocarditis and submitted these records for review by three of the authors, who are consultants in infectious diseases recognized for their expertise in infective endocarditis [5, 6]. These experts used their own global clinical judgment to classify potential cases as definite, probable, or possible cases or probable noncases. Agreement of two of the three reviewers was required to make the determination of a case or a noncase [6]. One control from the community was selected for each case-patient by using a modification of the Waksberg random-digit dialing method [7]. Controls and case-patients were matched for age (in 5-year strata), sex, and neighborhood of residence (by using area code, telephone exchange, and the first subsequent digit of the case-patients telephone number). We excluded from these analyses patients with infective endocarditis who were younger than 18 years of age, intravenous drug users, and patients who developed endocarditis in the hospital. This study received separate institutional review board approval at the University of Pennsylvania and all 54 participating hospitals. Data Collection Information was obtained from case-patients by conducting a structured telephone interview after hospital discharge. The date of hospital admission served as the study date for case-patients; for controls, the date of the telephone interview was used. Telephone interviewers collected information on demographic characteristics; diagnostic and therapeutic medical and dental procedures in the year before the study date; potential host risk factors, including preexisting cardiac lesions, preexisting local infection, risk factors for oral or dental disease, diabetes mellitus, immune deficiencies, family history of endocarditis, alcoholism, malignant conditions, and autoimmune disease; previous antibiotic use; and other recent illnesses. For each host risk factor, we requested the date of diagnosis, diagnostic method (for example, echocardiography for mitral valve prolapse), and the name of the practitioner who made the diagnosis. For each medical and dental procedure, we sought information about the procedure, the month and year in which it was performed, and the practitioner. We requested medical and dental records describing procedures and validating individual diagnoses. Study Variables Case-patients were considered infected with dental flora if the organism found was viridans streptococci; nutritionally variant streptococci; Actinobacillus species; Cardiobacterium hominis; anaerobes; -hemolytic streptococci (not group D); unspecified streptococci; or Haemophilus, Eikenella, Kingella, or Neisseria species. Because this study focused on indications for antibiotic prophylaxis, we examined host characteristics reported by patients as the primary risk factor variables, reflecting the information that would be available to a practitioner about to perform a procedure for which prophylaxis might be indicated. A variable called any valvular heart abnormality was defined as the presence of any of the following self-reported, preexisting conditions: mitral valve prolapse, congenital heart disease, history of rheumatic fever with heart involvement, prosthetic heart valve, previous episode of endocarditis, or other valvular heart disease. Dental visit information was obtained solely from dental records. Dental hygiene care was defined as preventive oral health services and therapeutic services, including coronal scaling and polishing. Consistent with AHA guidelines, invasive dental procedures were defined to include dental hygiene care, extractions, periodontal treatment (including scaling and root planing), endodontic treatment, mouth or gingival surgery, and treatment of tooth abscess. Noninvasive dental procedures were simple restorations, prosthetic and restorative dentistry, fluoride treatment, and other procedures (prosthetic services, including adjustments and suture removal). Unless otherwise specified, dental treatment refers to all dental treatment and is not limited to invasive procedures. Initial analyses focused on dental procedures performed at any time in the 3 months before the study date. Analyses were then narrowed to 2 months and 1 month before the study date. Time frames are approximate because the onset of infective endocarditis is often difficult to determine with certainty. We therefore chose the date of hospital admission as the study date, collected procedural data based on month rather than on a specific date, and calculated time frames under the assumption that procedures were performed on the 15th of the month. Statistical Analysis Frequencies and cross-tabulations between casecontrol status and potential risk factors were obtained. Conditional logistic regression was used to determine the independent effects of the various potential risk factors and the possibility of any interactions among factors [8]. Variables were included in multiple regression models if they were significant (P < 0.2) in unadjusted (matched) analyses (such as kidney disease and diabetes), if their inclusion had a substantial effect (>15% change) on coefficients for variables already in the model (such as insurance status) [9], or if they were strongly suspected a priori of being confounders (such as ethnicity). For analyses specific to participants with known cardiac valvular abnormalities, odds ratios and CIs were calculated from a model that included main effects for cardiac valvular abnormalities and dental treatment and the interaction between those variables. The odds ratio for various dental therapy variables among participants with cardiac valvular abnormalities was estimated by combining coefficients for the dental therapy variable and the interaction term. The CI for this combination of coefficients was estimated by using the appropriate variance and covariance terms [8]. With the interaction terms, participants with and those without valvular abnormalities were included in these analyses. Exact odds ratios and CIs, stratified on the matching variables, were calculated when data were too sparse for conditional logistic regression [10]. We used SAS statistical software (SAS Institute Inc, Cary, North Carolina) for data management and to obtain frequencies and cross-tabulations. We used EGRET (Epidemiological Graphics, Estimation and Testing software, version 0.25.1, Cytel Software Corp., Cambridge, Massachusetts) for conditional logistic regressions and exact analyses. All CIs are 95%, and all P values are two-sided. The sample size for the study was chosen so that by assuming an level of 0.05 (two-sided) and a power of 80%, we would be able to detect associations with an odds ratio of 2.0 or more for risk factors with a prevalence between 0.1 and 0.8. Results Participants We identified and recruited 416 potential case-patients (Figure 1). Our assessment process confirmed that more than 90% of true cases of infective endocarditis had been identified. The expert panel judged 379 patients to have definite, probable, or possible infective endocarditis; 37 (9%) were judged to be probable noncases and were excluded. Agreement among judgments was high, ranging from 92% to 96% [6]. Figure 1. Enrollment of case-patients. Of these 379 patients, 287 had community-acquired infective endocarditis not associated with intravenous drug use (248 on native valves and 39 on prosthetic valves), 27 had nosocomial infective endocarditis (18 on nativ


Clinical Infectious Diseases | 2005

Staphylococcus aureus Native Valve Infective Endocarditis: Report of 566 Episodes from the International Collaboration on Endocarditis Merged Database

Josù M. Miro; Ignasi Anguera; Christopher H. Cabell; Anita Y. Chen; Judith A. Stafford; G. Ralph Corey; Lars Olaison; Susannah J. Eykyn; Bruno Hoen; Elias Abrutyn; Didier Raoult; Arnold S. Bayer; Vance G. Fowler

BACKGROUND Staphylococcus aureus native valve infective endocarditis (SA-NVIE) is not completely understood. The objective of this investigation was to describe the characteristics of a large, international cohort of patients with SA-NVIE. METHODS The International Collaboration on Endocarditis Merged Database (ICE-MD) is a combination of 7 existing electronic databases from 5 countries that contains data on 2212 cases of definite infective endocarditis (IE). RESULTS Of patients with native valve IE, 566 patients [corrected] had IE due to S. aureus, and 1074 patients had IE due to pathogens other than S. aureus (non-SA-NVIE). Patients with S. aureus IE were more likely to die (20% vs. 12%; P < .001), to experience an embolic event (61% [corrected] vs. 31%; P < .001), or to have a central nervous system event (21% [corrected] vs. 13%; P < .001) and were less likely to undergo surgery (26% vs. 39%; P < .001) than were patients with non-SA-NVIE. Multivariate analysis of prognostic factors of mortality identified age (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.1-1.7), periannular abscess (OR, 2.4; 95% CI, 1.0 [corrected] -5.6), heart failure (OR, 3.9; 95% CI, 2.3-6.7), and absence of surgical therapy (OR, 2.3; 95% CI, 1.3-4.2) as variables that were independently associated with mortality in patients with SA-NVIE. After adjusting for patient-, pathogen-, and treatment-specific characteristics by multivariate analysis, geographical region was also found to be associated with mortality in patients with SA-NVIE (P < .001). CONCLUSIONS S. aureus is an important and common cause of IE. The outcome of SA-NVIE is worse than that of non-SA-NVIE. Several clinical parameters are independently associated with mortality for patients with SA-NVIE. The clinical characteristics and outcome of SA-NVIE vary significantly by geographic region, although the reasons for such regional variations in outcomes of SA-NVIE are unknown and are probably multifactorial. A large, prospective, multinational cohort study of patients with IE is now under way to further investigate these observations.


Experimental Gerontology | 2002

Role of humoral and cell-mediated immunity in protection from influenza disease after immunization of healthy elderly

Donna M. Murasko; Erica D. Bernstein; Elizabeth M. Gardner; Peter Gross; Gary Munk; Sandra Dran; Elias Abrutyn

While influenza immunization significantly reduces the risk of pneumonia and associated deaths, vaccination of elderly only affords 30-50% protection against influenza disease. The purpose of this study was to: (1) evaluate the consistency of immune responses across multiple years in young and elderly; (2) determine the contribution of antibody and cell-mediated responses in protection after immunization with influenza vaccine. Independently living healthy elderly (>200/year; mean age 78.8-80.6/year) were recruited yearly in this four year study. The results clearly demonstrate: (1) both young and elderly consistently produced significant antibody and T cell proliferative responses to influenza vaccine upon yearly immunization; however, both responses of elderly were significantly and consistently lower than young. (2) Percentages of both young and elderly demonstrating protective titers (i.e. HI>/=40) increased post-immunization each year, but were consistently higher in young compared to elderly. (3) The risk of developing influenza disease after immunization was highest among elderly demonstrating neither antibody nor cell-mediated responses. Importantly, the risk of influenza disease was comparable in elderly demonstrating a cell-mediated response alone, an antibody response alone, or both cell-mediated and antibody responses. This suggests that cell-mediated responses play a significant role in protection in at least a subset of elderly from influenza disease after immunization.


Clinical Infectious Diseases | 2009

Initial Low-Dose Gentamicin for Staphylococcus aureus Bacteremia and Endocarditis Is Nephrotoxic

Sara E. Cosgrove; Gloria Vigliani; Marilyn Campion; Vance G. Fowler; Elias Abrutyn; G. Ralph Corey; Donald P. Levine; Mark E. Rupp; Henry F. Chambers; Adolf W. Karchmer; Helen W. Boucher

BACKGROUND The safety of adding initial low-dose gentamicin to antistaphylococcal penicillins or vancomycin for treatment of suspected Staphylococcus aureus native valve endocarditis is unknown. This study evaluated the association between this practice and nephrotoxicity. METHODS We performed a prospective cohort study of safety data from a randomized, controlled trial of therapy for S. aureus bacteremia and native valve infective endocarditis involving 236 patients from 44 hospitals in 4 countries. Patients either received standard therapy (antistaphylococcal penicillin or vancomycin) plus initial low-dose gentamicin (n=116) or received daptomycin monotherapy (n = 120). We measured renal adverse events and clinically significant decreased creatinine clearance in patients (1) in the original randomized study arms and (2) who received any initial low-dose gentamicin either, as a study medication or <or= days before enrollment. RESULTS Renal adverse events occurred in 8 (7%) of 120 daptomycin recipients, 10 (19%) of 53 vancomycin recipients, and 11 (17%) of 63 antistaphylococcal penicillin recipients. Decreased creatinine clearance occurred in 9 (8%) of 113 of evaluable daptomycin recipients, 10 (22%) of 46 vancomycin recipients, and 16 (25%) of 63 antistaphylococcal penicillin recipients. An additional 21 patients received initial low-dose gentamicin <or=2 days before study enrollment. A total of 22% of patients who received initial low-dose gentamicin versus 8% of patients who did not receive initial low-dose gentamicin experienced decreased creatinine clearance (P = 005 ). Independent predictors of a clinically significant decrease in creatinine clearance were age >or=65 years and receipt of any initial low-dose gentamicin. CONCLUSIONS Initial low-dose gentamicin as part of therapy for S. aureus bacteremia and native valve infective endocarditis is nephrotoxic and should not be used routinely, given the minimal existing data supporting its benefit.


The American Journal of Medicine | 1986

Epidemiology of bacteriuria in an elderly ambulatory population

Jerome A. Boscia; William D. Kobasa; Ralph Knight; Elias Abrutyn; Matthew E. Levison; Donald Kaye

This study of bacteriuria in elderly (mean age 85 years, range 68 to 103) Jewish subjects of mostly middle and upper class attempted to determine disease prevalence, define the turnover in infected subjects, and assess the relation between functional status and infection. The prevalence of bacteriuria (midstream clean-catch method) was assessed in 373 women and 150 men. It was higher in women (18.2 percent) than in men (6.0 percent) (p less than 0.001) and was more common in functionally impaired nursing home residents (23.5 percent) than in apartment house dwellers (12.1 percent) (p less than 0.01). In longitudinal studies, 260 subjects (184 women and 76 men) had three urine culture surveys at six-month intervals. The cumulative percent infected on at least one survey was high (women 30.4 percent, men 10.5 percent). However, persistence of the same organism on all three surveys was surprisingly infrequent (women 6.0 percent, men 1.3 percent), and the turnover of infected and noninfected subjects was considerable. Persistence of bacteriuria on all three surveys was significantly more common in nursing home residents (13.9 percent) than in apartment house dwellers (3.1 percent) (p less than 0.01). Thus, bacteriuria is common in the elderly and appears related to functional status. However, the turnover of infected and noninfected subjects was high, and surprisingly, persistence was not found in most. The transient nature of bacteriuria in most provides support against the treatment of asymptomatic bacteriuria in the elderly.


Circulation | 2000

Risk Factors for Infective Endocarditis Oral Hygiene and Nondental Exposures

Brian L. Strom; Elias Abrutyn; Jesse A. Berlin; Judith L. Kinman; Roy S. Feldman; Paul D. Stolley; Matthew E. Levison; Oksana M. Korzeniowski; Donald Kaye

Background—The risks of infective endocarditis (IE) associated with various conditions and procedures are poorly defined. Methods and Results—This was a population-based case-control study conducted in 54 Philadelphia, Pa–area hospitals from 1988 to 1990. Community-acquired IE cases unassociated with intravenous drug use were compared with matched community residents. Subjects were interviewed for risk factors. Diagnoses were confirmed by expert review of medical record abstracts with risk factor data removed. Cases were more likely than controls to suffer from prior severe kidney disease (adjusted OR [95% CI]=16.9 [1.5 to 193], P =0.02) and diabetes mellitus (adjusted OR [95% CI]=2.7 [1.4 to 5.2], P =0.004). Cases infected with skin flora had received intravenous fluids more often (adjusted OR [95% CI]=6.7 [1.1 to 41], P =0.04) and had more often had a previous skin infection (adjusted OR [95% CI]=3.5 [0.7 to 17], P =0.11). No association was seen with pulmonary, gastrointestinal, cardiac, or genitourinary procedures or with surgery. Edentulous patients had a lower risk of IE from dental flora than patients who had teeth but did not floss. Daily flossing was associated with a borderline decreased IE risk. Conclusions—Within the limits of the available sample size, the data showed that IE patients differ from people without IE with regard to certain important risk factors but not regarding recent procedures.


Vaccine | 1999

Immune response to influenza vaccination in a large healthy elderly population

Erica D. Bernstein; D Kaye; Elias Abrutyn; Peter Gross; M Dorfman; Donna M. Murasko

Elderly individuals not only demonstrate a greater risk of morbidity and mortality from influenza than the young, but also have greater difficulty mounting a protective response to influenza vaccine. The mechanism of the decreased efficacy of influenza vaccination in the elderly is not well understood. The present study was designed to assess the interaction between cell-mediated and humoral immune responses to influenza vaccine in a large population (n = 233) of healthy elderly individuals (mean age = 80.7) living in six continuing care retirement communities (CCRCs). While influenza vaccination resulted in significant increases in the mean anti-influenza antibody titres and mean proliferative responses of peripheral blood mononuclear cells to purified subvirion trivalent influenza vaccine one month after vaccination, only 48.9% and 30.0% of subjects had intact humoral and cell-mediated immune responses, respectively. No association was observed between intact cell-mediated and humoral responses: 14.7% of subjects had an intact cell-mediated, but not humoral response, and 32.6% of subjects had an intact humoral, but not cell-mediated response. However, IFNgamma production was significantly correlated with both antibody and cell-mediated responses to influenza vaccination, a finding not previously reported in the elderly. These results indicate that there is considerable heterogeneity among immune responses of the elderly to influenza vaccination. This heterogeneity needs to be a major consideration in evaluation of new vaccine preparations.


Annals of Internal Medicine | 1994

Does Asymptomatic Bacteriuria Predict Mortality and Does Antimicrobial Treatment Reduce Mortality in Elderly Ambulatory Women

Elias Abrutyn; Jana Mossey; Jesse A. Berlin; Jerome A. Boscia; Matthew E. Levison; Peter G. Pitsakis; Donald Kaye

Asymptomatic bacteriuria, a common problem of the elderly, has been associated with increased mortality in the elderly [1-4], although not all studies have confirmed this finding [5-9]. To reconcile these conflicting results, we did a longitudinal study of urinary tract infection in ambulatory elderly women to evaluate the putative relation between asymptomatic bacteriuria and mortality. We considered resolution of this issue to be important because of the implications for clinical practice. If asymptomatic bacteriuria were shown to be an independent risk factor for mortality and if it could also be shown that eradication of the infection by antimicrobial therapy decreased the risk for death, then screening and antimicrobial treatment of elderly ambulatory women with asymptomatic bacteriuria might be warranted and the cost of identifying and treating such infections might be justified. Conversely, failure to confirm a relation would support the view that programs to screen for bacteriuria would not be justified if their goal was to enhance survival. This report summarizes the findings of our 9-year study to determine whether asymptomatic bacteriuria in elderly ambulatory women is a marker of increased mortality and, if so, whether it is because of an association with other determinants of mortality or because asymptomatic bacteriuria is itself an independent cause, the removal of which might improve longevity. The components of the study were a longitudinal study in elderly ambulatory women to compare mortality in those with and without asymptomatic bacteriuria and a double-blind, controlled clinical trial in which antimicrobial therapy was administered for asymptomatic bacteriuria to assess whether treatment decreases mortality. Methods Participant enrollment and the participating institutions have been described previously [10, 11]. Elderly ambulatory residents of the Philadelphia Geriatric Center and of 21 continuing care retirement communities in the greater Philadelphia metropolitan area who gave informed consent were enrolled in this long-term study of urinary tract infection in the elderly. Enrollment continued throughout the course of the study. Philadelphia Geriatric Center houses about 1000 residents who primarily are Jewish; incomes are higher than the maximum Social Security payment; and congregate living is provided either in an apartment house or in a nursing home. In contrast, the continuing care retirement communities are smaller (bed size range, 108 to 675); incomes are higher; residents are primarily not Jewish; and a higher proportion of residents are fully independent. All female residents were eligible to participate except those with indwelling catheters or those incapable of providing midstream clean-catch urine specimens for culture. Specimens were obtained on enrollment and every 6 months thereafter. The protocol was approved by the appropriate institutional review boards, and informed consent was obtained from the participants or their surrogates. Table 1 shows the study periods and chronology of important study events. Throughout the study, urine cultures were obtained at about 6-month intervals. An observational study to compare mortality of bacteriuric and nonbacteriuric volunteers regardless of treatment status was begun in January 1983 and ended in February 1992. Initially, residents with asymptomatic bacteriuria were identified and followed, but treatment was not given. However, on 10 October 1983, a controlled clinical trial was begun to evaluate whether antimicrobial therapy for asymptomatic bacteriuria decreased mortality; every bacteriuric study participant identified after this date was enrolled in the trial. Mortality among residents who were treated with antimicrobial agents for asymptomatic bacteriuria each time it was present was compared with the mortality of those who received no therapy for their episodes of bacteriuria. At enrollment, participants were assigned to the treatment group or to the control group based on the last digit of an identification number unrelated to the conduct of the study. Urine cultures were read by personnel blinded to the study group assignment. When asymptomatic bacteriuria was identified, participants with even numbers were given antimicrobial therapy according to a defined protocol (see below); those with odd numbers served as controls. From 10 October 1983 to 10 December 1987, controls were given no therapy. Thereafter, on the advice of external consultants, the protocol was changed so that participants not assigned to the active treatment group were given placebo pills in place of no treatment. The placebo pills were identical in appearance to each of the antimicrobial agents used. Thus, after 10 December 1987, volunteers with asymptomatic bacteriuria were given therapy in either the form of antimicrobics or placebo after a new consent was obtained; the volunteers and clinical personnel did not know study group assignments. Table 1. Study Design and Enrollment The methods for collecting first-morning urine and for processing the specimens in our research microbiology laboratory have been previously described [10, 11]. Participants were considered to have asymptomatic bacteriuria on a survey if two urine specimens were culture-positive (105 colony-forming units or more per mL of urine) for the same organism within 2 weeks. From 10 October 1983 through 10 December 1987, residents with asymptomatic bacteriuria who were assigned to receive antimicrobial treatment were given short-course therapy (single dose or 3 days) as follows: trimethoprim, 200 mg in one dose; trimethoprim-sulfamethoxazole, 1 double-strength tablet; cefaclor, 500 mg three times a day for 3 days; amoxicillin, 250 mg three times a day for 3 days; carbenicillin indanyl sodium, four times a day for 3 days; or macrodantin, 100 mg twice a day for 3 days, depending on susceptibility of the infecting organism and history of drug allergy. Participants were considered cured if test-of-cure cultures contained less than 104 colony-forming units/mL of the infecting organism on cultures obtained 5 to 10 days after antimicrobial treatment or placebo or on cultures obtained on the next survey in those receiving no therapy. When positive for the same organism, patients were retreated for 14 days with test-of-cure culture afterward. If the organism differed, reinfection was diagnosed and a single dose or 3-day therapy was used; treatment failures were treated as defined above. Test-of-cure cultures were obtained again after therapy and, if positive for the same organism, participants were treated for 14 days. No treatment was given after failure of a 14-day course or two reinfections after short courses. Controls received no therapy during this period. After 10 December 1987, culture-positive patients were assigned to antimicrobial treatment or placebo. Single-dose therapy was given with trimethoprim, 200 mg, or norfloxacin, 400 mg, depending on the susceptibility of the organism; the same drugs (trimethoprim, 100 mg twice daily, and norfloxacin, 400 mg twice daily) were used for 14 days of therapy in patients failing single-dose therapy. Single-dose therapy was used for reinfection. The placebo pills and regimen given to a placebo recipient matched the regimen administered to the participant in the active treatment group who was treated most recently (for example, if the active treatment participant received short-course trimethoprim followed by 14 days of trimethoprim, the next placebo participant received short-course trimethoprim placebo followed by 14 days of trimethoprim placebo). Symptomatic infections were managed by the participants personal physician or by physicians associated with the facility in which the patient lived. Reports were received on an annual or semiannual basis from the participating institutions that detailed changes in their census. All deaths were noted, and registry coordinators reviewed available documents to confirm each death. After 1 September 1987, detailed functional and mental status assessments were done when persons were newly enrolled into the study or were seen for an annual follow-up visit using techniques previously described [11, 12]. Self-care activities of daily living were assessed by a modification of the Multilevel Assessment Instrument [13], and mental status was assessed using a modified version of the Kahn and Goldfarb questionnaire [14]. A subjective measure of global health status (scale, 1 to 4) was based on responses to the question: How do you rate your health: excellent (score 1), good, fair, and bad or poor (score 4)? Diagnoses recorded in the persons medical record were extracted and provided a more objective measure of health status; they were coded according to the ICD-9-CM three-digit codes [15]. The Geriatric Depression Scale [16] was used to assess depressive symptoms, and walking ability was assessed on a scale of 1 (specialized help needed) to 3 (help not needed) [11]. Statistical Analysis Observational Study These analyses compared residents with asymptomatic bacteriuria with residents who did not have asymptomatic bacteriuria on any of the urine culture surveys done during the period of their participation. For the purposes of the survival analyses in the observational study, the results of urine cultures were considered a time-dependent covariate. Accordingly, participants were considered in the ever-positive group once asymptomatic bacteriuria was identified, and all subsequent time on study was contributed to the group with positive cultures regardless of urine culture results on subsequent surveys. Persons entering the study with a negative urine culture were considered in the never-positive group until asymptomatic bacteriuria was identified. Thus, a person who entered the study with negative cultures and who later became culture-positive would have contributed person-time to the follow-up of those in the categ


The American Journal of Medicine | 1986

A lack of association between bacteriuria and symptoms in the elderly

Jerome A. Boscia; William D. Kobasa; Elias Abrutyn; Matthew E. Levison; Adele M. Kaplan; Donald Kaye

In a study of bacteriuria in elderly (mean age 85 years, range 69 to 101), mostly middle- and upper-class Jewish subjects, attempts were made to determine if bacteriuria without dysuria is otherwise asymptomatic. Seventy-two subjects (59 women and 13 men) without dysuria were questioned about other urinary symptoms (incontinence, frequency, urgency, suprapubic pain, flank pain, fever) and symptoms indicating a lack of well-being (anorexia, difficulty in falling asleep, difficulty in staying asleep, fatigue, malaise, weakness) when they were with and without bacteriuria. Twenty-two subjects had bacteriuria that resolved spontaneously; bacteriuria subsequently developed in 24 nonbacteriuric subjects; and 26 subjects had bacteriuria that resolved with antimicrobial therapy. Subjects occasionally reported urinary symptoms (especially incontinence) and commonly reported symptoms indicating a lack of well-being when they were with and/or without bacteriuria. However, no differences in symptoms were found when bacteriuric subjects were compared with themselves when they were nonbacteriuric. Thus, bacteriuria without dysuria in the elderly appears to be asymptomatic.

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Jesse A. Berlin

University of Pennsylvania

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