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Editorial. Comments on a preliminary report describing a possible beneficial effect of extracorporeal photopheresis in patients with AIDS-related complex. Justification for the experiment; Trials conducted on the patients; Limitations of the observational study.

Editorial. Highlights the recommendations from the American Heart Association (AHA) on the prevention of bacterial endocarditis which were published in December 1990. Facts and assumptions that underpin the recommendations; Rationale of the AHA recommendations; Main prophylactic regimens recommended for genitourinary and gastrointestinal procedures.

Presents a study which examined the occurrence of pyuria and asymptomatic bacteriuria in elderly ambulatory women. Overview of previous studies on pyuria and bacteriuria in the elderly; Definition of low-titer bacteriuria; Correlation of pyuria with various levels of bacteriuria.

Discusses the effects of potential toxicants on the immune system. Examples of substances in the environment which have immunosuppressive properties; Background on a 1978 symposium held by the U.S. Federal Drug Administration regarding immunotoxicity; Dimensions in which immunotoxicology must be developed.

Presents abstracts of articles published in the January 9, 1999 issue of the periodical 'British Dental Journal.'

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=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.

Background: Embolic events to the central nervous system are a major cause of morbidity and mortality in patients with infective endocarditis (IE). The appropriate role of valvular surgery in reducing such embolic events is unclear. The purpose of this study was to determine the relationship between the initiation of antimicrobial therapy and the temporal incidence of stroke in patients with IE and to determine if this time course differs from that shown for embolic events in previous studies., Methods: Prospective incidence cohort study involving 61 tertiary referral centers in 28 countries. Case report forms were analyzed from 1437 consecutive patients with left-sided endocarditis admitted directly to participating centers., Results: The crude incidence of stroke in patients receiving appropriate antimicrobial therapy was 4.82/1000 patient days in the first week of therapy and fell to 1.71/1000 patient days in the second week. This rate continued to decline with further therapy. Stroke rates fell similarly regardless of the valve or organism involved. After 1 week of antimicrobial therapy, only 3.1% of the cohort experienced a stroke., Conclusions: The risk of stroke in IE falls dramatically after the initiation of effective antimicrobial therapy. The falling risk of stroke in patients with IE as a whole precludes stroke prevention as the sole indication for valvular surgery after 1 week of therapy.

Infective endocarditis (IE) remains a serious and deadly disease. The incidence, which varies by gender and on the presence of predisposing factors, has not decreased, due in part to the aging population with more healthcare exposures and predisposing risk factors such as prosthetic heart valves and intracardiac devices. The most important aspects of treatment in IE hinge upon early diagnosis, microorganism identification with susceptibility testing, and early initiation of appropriate antibiotic therapy. In addition, echocardiographic imaging is critical for both diagnostic and prognostic purposes. Early evaluation for surgery should be considered. Once a therapeutic strategy is begun, careful attention to the clinical course is necessary to ensure appropriate response to therapy and to identify complications early.

Background: Influenza vaccination has been shown to reduce illness and all-cause mortality in vulnerable populations through the prevention of influenza infection. Attenuation of the severity of illness by vaccination has been reported for respiratory tract infections due to bacterial pathogens and would represent an important additional health benefit of influenza vaccination. We evaluated the impact of prior influenza vaccination on in-hospital mortality and other health outcomes among hospitalized adults with community-acquired pneumonia (CAP)., Methods: Consecutive individuals hospitalized with CAP during "influenza season" (November to April, 1999-2003) at hospitals operated by Tenet HealthCare were identified using a database constructed to improve quality of patient care. Associations between vaccination status and all-cause in-hospital mortality were evaluated using logistic regression models., Results: Among 17 393 adults hospitalized with CAP during the study period, 1590 (19% of those with recorded vaccine status) had a history of influenza vaccination in the current or most recent influenza season. Vaccine recipients were less likely to die in hospital of any cause than individuals without vaccination (odds ratio, 0.30; 95% confidence interval, 0.22-0.41). These effects remained significant after adjustment for the presence of comorbid illnesses and pneumococcal vaccination (adjusted odds ratio for death, 0.61; 95% confidence interval, 0.43-0.87) and under widely varying assumptions about individuals with missing vaccination status., Conclusions: Prior influenza vaccination was associated with improved survival in hospitalized patients with CAP during influenza season. This observation, if confirmed by other studies, would represent an important additional benefit of enhanced influenza vaccine coverage.

Propionibacterium species are occasionally associated with serious systemic infections such as infective endocarditis. In this study, we examined the clinical features, complications and outcome of 15 patients with Propionibacterium endocarditis using the International Collaboration on Endocarditis Merged Database (ICE-MD) and Prospective Cohort Study (ICE-PCS), and compared the results to 28 cases previously reported in the literature. In the ICE database, 11 of 15 patients were male with a mean age of 52 y. Prosthetic valve endocarditis occurred in 13 of 15 cases and 3 patients had a history of congenital heart disease. Clinical findings included valvular vegetations (9 patients), cardiac abscesses (3 patients), congestive heart failure (2 patients), and central nervous system emboli (2 patients). Most patients were treated with beta-lactam antibiotics alone or in combination for 4 to 6 weeks. 10 of the 15 patients underwent valve replacement surgery and 2 patients died. Similar findings were noted on review of the literature. The results of this paper suggest that risk factors for Propionibacterium endocarditis include male gender, presence of prosthetic valves and congenital heart disease. The clinical course is characterized by complications such as valvular dehiscence, cardiac abscesses and congestive heart failure. Treatment may require a combination of medical and surgical therapy.

Background: Although surgical intervention is often used in the treatment of prosthetic valve infective endocarditis (PVIE), an understanding of its effect on survival has been limited by the biases of observational studies and lack of controlled trials., Methods: The International Collaboration on Endocarditis Merged Database is a large, multicenter, international registry of patients with definite endocarditis by Duke criteria, including 367 patients with PVIE. Clinical, microbiologic, and echocardiographic variables were analyzed to determine those factors associated with the use of surgery for PVIE. Logistic regression analysis was performed to create a propensity model of predictors of surgery use. Patients who underwent surgery during initial hospitalization were matched by propensity score with patients treated with medical therapy alone. Logistic regression analysis was performed to determine variables independently associated with inhospital mortality in this matched subset., Results: Surgical therapy for PVIE was performed in 148 (42%) of 367 patients. Inhospital mortality was similar for patients treated with surgery compared with those treated with medical therapy alone (25.0% vs 23.4%, P = .729). Surgical therapy was independently associated with patient age, microorganism, intracardiac abscess, and congestive heart failure. After adjustment for these determinants, inhospital mortality was predicted by brain embolization (OR 11.12, 95% CI 4.16-29.73) and Staphylococcus aureus infection (OR 3.67, 95% CI 1.29-9.74), with a trend toward benefit for surgery (OR 0.56, 95% CI 0.23-1.36)., Conclusions: Despite the frequent use of surgery for the treatment of PVIE, this condition continues to be associated with a high inhospital mortality rate in the contemporary era. After adjustment for factors related to surgical intervention, brain embolism and S aureus infection were independently associated with inhospital mortality and a trend toward a survival benefit of surgery was evident.

Background: Early surgery has been shown to be beneficial for patients with infective endocarditis (IE), yet surgery is not used in most patients. Evidence of the uncertainty around the use of surgery can be found in the wide variations in the use of cardiac surgery in IE with few precise indications for cardiac surgery yet defined. The aim of the study was to characterize patients with native valve IE relative to surgery and to determine if patients who benefit from an early surgical intervention can be identified., Methods: The International Collaboration on Endocarditis Merged Database was used to quantify the differences between patients with IE receiving medical and surgical intervention in 1516 patients with definite native valve IE. Propensity models were built to identify a group of patients that benefit from early surgery., Results: Patients in the early surgical group were more likely to be male, younger, and with less comorbidities compared with the early medical group (P < .001 for all) and were less likely to have infection with Staphylococcus aureus or viridans group streptococci (P < .05 for all). Intracardiac abscess and heart failure were much more common in the surgical group (P < .001 for all). In an unadjusted comparison, there was no statistically significant survival advantage in the surgical group. However, in the propensity analysis, in the subgroup of patients with the most indications for surgery, there was a significant decrease in mortality associated with early surgery (11.2% vs 38.0%, P < .001)., Conclusions: The benefits of surgery are not seen uniformly in all patients with native valve IE, but are most realized in a targeted population. This observation requires confirmation in other populations of patients with definite IE.

The aims of this study were to determine the clinical characteristics and outcome of patients who had definite infective endocarditis (IE) complicated by aortic ring abscess formation that was detected with transesophageal echocardiography (TEE) and to determine the prognostic significance of abscess formation in aortic valve IE. Patients who had aortic valve IE were selected from the International Collaboration on Endocarditis Merged Database (ICE-MD) if they underwent TEE. Among 311 patients who had definite aortic valve IE, 67 (22%) had periannular abscesses. They were more likely to have infection in the setting of a prosthetic valve (40% vs 19%, p <0.001) and coagulase-negative staphylococcal IE (18% vs 6%, p < 0.01) and less likely to have streptococcal IE than were patients who did not develop abscess (28% vs 46%, p = 0.01). Systemic embolization, central nervous system events, and heart failure did not differ between those who developed abscess and those who did not, but power was limited. Patients who had abscess were more likely to undergo surgery (84% vs 36%, p <0.001), and their in-hospital mortality rate was higher (19% vs 11%, p = 0.09). Multivariate analysis of prognostic factors of mortality in aortic IE identified age (odds ratio [OR] 1.6, 95% confidence interval [CI]1.2 to 2.1), Staphylococcus aureus (S. aureus) infection (OR 2.4, 95% CI 1.1 to 5.2), and heart failure (OR 2.9, 95% CI 1.4 to 6.1) as variables that were independently associated with increased risk of death. Periannular abscess formation showed a nonsignificant trend toward an increased risk of death (OR 1.9, 95% CI 0.9 to 3.8). Multivariate analysis of prognostic factors of mortality in complicated aortic IE with abscess formation identified S. aureus infection (OR 6.9, 95% CI 1.6 to 29.4) as independently associated with increased risk of death. In conclusion, in the current era of TEE and high use of surgical treatment, periannular abscess formation in aortic valve IE is not an independent risk factor for mortality. S. aureus infection is an independent prognostic factor for mortality in patients who have abscess formation.

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.

Context: The global significance of infective endocarditis (IE) caused by Staphylococcus aureus is unknown., Objectives: To document the international emergence of health care-associated S aureus IE and methicillin-resistant S aureus (MRSA) IE and to evaluate regional variation in patients with S aureus IE., Design, Setting, and Participants: Prospective observational cohort study set in 39 medical centers in 16 countries. Participants were a population of 1779 patients with definite IE as defined by Duke criteria who were enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study from June 2000 to December 2003., Main Outcome Measure: In-hospital mortality., Results: S aureus was the most common pathogen among the 1779 cases of definite IE in the International Collaboration on Endocarditis Prospective-Cohort Study (558 patients, 31.4%). Health care-associated infection was the most common form of S aureus IE (218 patients, 39.1%), accounting for 25.9% (Australia/New Zealand) to 54.2% (Brazil) of cases. Most patients with health care-associated S aureus IE (131 patients, 60.1%) acquired the infection outside of the hospital. MRSA IE was more common in the United States (37.2%) and Brazil (37.5%) than in Europe/Middle East (23.7%) and Australia/New Zealand (15.5%, P<.001). Persistent bacteremia was independently associated with MRSA IE (odds ratio, 6.2; 95% confidence interval, 2.9-13.2). Patients in the United States were most likely to be hemodialysis dependent, to have diabetes, to have a presumed intravascular device source, to receive vancomycin, to be infected with MRSA, and to have persistent bacteremia (P<.001 for all comparisons)., Conclusions: S aureus is the leading cause of IE in many regions of the world. Characteristics of patients with S aureus IE vary significantly by region. Further studies are required to determine the causes of regional variation.

Using a large cohort of patients from the International Collaboration on Endocarditis Merged Database, we compared coagulase-negative staphylococcal (CoNS) native-valve endocarditis (NVE) to NVE caused by more common pathogens. Rates of heart failure and mortality were similar between patients with CoNS NVE and patients with Staphylococcus aureus NVE, but rates for both groups were significantly higher than rates for patients with NVE due to viridans streptococci. These results emphasize the importance of CoNS as a cause of NVE and the potential for serious complications with this infection.

Resistance to antimicrobial drugs is increasing at an alarming rate among both gram-positive and gram-negative bacteria. Traditionally, bacteria resistant to multiple antimicrobial agents have been restricted to the nosocomial environment. A disturbing trend has been the recent emergence and spread of resistant pathogens and resistance traits in nursing homes, the community, as well as in hospitals. This article reviews the epidemiology, molecular mechanisms of resistance, and treatment options for pathogens resistant to antimicrobial drugs.

Candida infective endocarditis (IE) is increasingly common, yet most reports have been single-center reviews. We evaluated 16 patients with Candida IE nested within a cohort of 2,022 patients with IE. Prosthetic valve IE was more common in patients with Candida (50% vs 17%); mortality was 37% for patients with Candida.

In the century and a quarter since William Osler delivered his famed Gulstonian lectures on endocarditis, continual advancements have been made in understanding and treating this disease. Here we have reviewed some key aspects of current knowledge in the areas of population epidemiology, host factors, microorganisms, and diagnosis. The advent of the ICE investigation provides the opportunity to further expand our understanding of IE by developing a very large, global database of IE patients whose clinical, echocardiographic, and microbiologic findings have been characterized with standard methodology. Further, ICE may serve as a rich source of material for investigators seeking to perform specific studies. Finally, the ICE infrastructure creates the opportunity for performing randomized trials to test therapeutic strategies. Although many obstacles remain to be overcome, ICE has created the opportunity for a quantum leap in our knowledge of IE over the next 25 years.

Itch is a subjective symptom; its magnitude (intensity) may be only estimated by the reports of patients or volunteers. We utilized a comparative screening method to identify and quantify the efficacy of topical antipruritics with a histamine-induced itch human model. Ten individuals responsive to histamine-induced itch sensation were enrolled. Both forearms served as test sites. Each test site was treated randomly either by histamine injection only or pretreated with a coded candidate formula for 30 min and then a histamine injection. Itch was experimentally induced in each test site by the intracutaneous injection of 100 microg histamine dihydrochloride dissolved in 1 ml normal saline. Itch magnitude was measured each minute after histamine injection for 20 min with a magnitude visual analogue scale. Itch duration was also recorded. Formulation D significantly (p < 0.05) decreased itch magnitude (within a 20-min test period), from 2.6 +/- 2.1 cm (mean +/- SD) to 2.2 +/- 2.1 cm (mean +/- SD) when compared to its vehicle control; it also significantly (p < 0.05) shortened itch duration (15.0 +/- 7.4 min; mean +/- SD) in comparison with its vehicle control (20.3 +/- 7.0 min; mean +/- SD). Of all the formulations tested, formulation D was the most effective antipruritic in decreasing histamine-induced itch. This method may act as a simple and robust screening procedure when evaluating potential antipruritics and allow a comparison among products. Until validated with disease-induced itch, e.g., atopic dermatitis, the model should be considered screening in nature., (Copyright 2002 S. Karger AG, Basel)

In the century and a quarter since William Osler delivered his framed lectures on endocarditis substantial advancements have occurred in the understanding and treatment of this disease. This article summarizes current understanding of endocarditis in the areas of population epidemiology, host factors, microorganisms, diagnosis, and therapy. In addition, the authors discuss possible directions for investigation in the future, including a new multinational consortium, the International Collaboration on Endocarditis (ICE). This collaboration aims to provide a mechanism to advance the understanding of endocarditis in areas difficult to study without an established network. The multinational nature of the collaboration may also permit a more global view of IE and provide opportunities for studies such as randomized trials of therapeutic treatment strategies.

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.

The effects of yearly influenza immunization on the level of antibody responses were assessed in 92 healthy elderly subjects immunized over four contiguous years (1993-1996) with a trivalent influenza vaccine that included A/Texas annually. Anti-A/Texas antibodies increased significantly and similarly post-vaccination each year, but returned to comparable baseline levels annually. Percentages of subjects with anti-A/Texas titers > or =40 post-vaccination were comparable over four years. Importantly, post-vaccination titers > or =40 to A/Texas in 1993-1994 predicted anti-A/Texas titers > or =40 in subsequent years. Thirty percent of individuals produced four-fold rises to any vaccine component the first year it was included in the vaccine, however, this percentage decreased to about 10% after subsequent vaccination with the same component. This study clearly supports the concept that annual immunization with the same influenza vaccine component over multiple years does not significantly decrease antibody titers in a healthy elderly population.

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.

The emergence of resistance to antimicrobial agents continues to be a major problem in the nosocomial setting and now in nursing homes and the community as well. Bacteria use a variety of strategies to avoid the inhibitory effects of antibiotic agents and have evolved highly efficient means for the dissemination of resistance traits. Control of antibiotic-resistant pathogens provides a major challenge for both the medical community and society in general. To control the emergence of resistant pathogens, CDC and infection control guidelines must be adhered to, and antibiotics must be used more judiciously.

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.

Prevention of infective endocarditis is a priority because this disease is associated with considerable morbidity and mortality both during the acute phase of the illness and subsequently, despite modern medical and surgical treatment. The American Heart Association has published recommendations for prevention by antimicrobial prophylaxis since 1955; the most recent revision of these guidelines appeared in 1997. All practicing physicians should know their content and understand their underlying concepts and assumptions.

Influenza vaccination is less efficacious in the elderly than in the young. To characterize this age-related decrease in immune response to influenza vaccination, antibody and cell-mediated responses to influenza vaccine were assessed before immunization and 4 weeks after vaccination of a population of 270 healthy elderly individuals (mean age: 80.2 years) living in eight local continuing care retirement communities (CCRCs) and 30 young individuals (mean age: 27.8 years). The antibody titres produced against all three influenza strains increased significantly after vaccination in both the young and elderly (p < 0.0005); however, the young demonstrated significantly higher titres to all three strains than did the elderly (p < 0.03). Peripheral blood mononuclear cells (PBMC) cultured with influenza vaccine demonstrated significantly increased proliferation (elderly: p < 0.00005; young: p < 0.001) after vaccination, with proliferative responses in the young significantly higher than the elderly both before (p < 0.04) and after (p < 0.0005) vaccination. Similarly, IFN gamma production in these PBMC cultures increased significantly pre- to postvaccination in both young and elderly (young: p < 0.006; elderly: p < 0.00005), but the young produced more than the elderly both pre- and postvaccination (p < 0.0001). Following vaccination, PBMC production of IL-10 was higher in the young than in the elderly (p < 0.0015), while IL-6 production was comparable in both young and elderly individuals. Greater than 13% of the elderly population did not produce detectable IL-6, IL-10, or IFN gamma either before or after vaccination. The data show that the decreased cell-mediated and humoral responses to influenza vaccination of this healthy elderly population are accompanied by the production of lower levels of cytokines. A unique finding in this population of 270 healthy elderly was the association between a TH0 cytokine profile and intact immune responses to influenza vaccine. A similar relationship was not seen in the young.

Urinary tract infection is common among older adults, although most individuals are asymptomatic. The prevalence of bacteriuria varies significantly with living situation and functional status. Asymptomatic bacteriuria is a benign condition and is not an independent risk factor for mortality in older adults. Treatment of asymptomatic bacteriuria generally is not indicated, but symptomatic urinary tract infection of the lower or upper tract dictates antibiotic therapy.

We evaluated the usefulness of the Duke criteria for diagnosing cases of active infective endocarditis (IE). Patients were identified prospectively over a 3-year period at 54 hospitals in the Philadelphia metropolitan area. Three of us independently reviewed abstracted hospital records and classified 410 patients as definite, probable, or possible cases of IE or as probable noncases. We then applied the Duke criteria to this sample to assess the degree of agreement between our diagnoses and the diagnoses based on these new criteria. Agreement was good to excellent, ranging from 72% to 90%, depending on the case definition used. The sensitivity of the Duke criteria was also good to excellent, varying from 71% to 99%, again depending on case definition used. Specificity was lower (0-89%). We conclude that use of the Duke criteria will result in little underdiagnosis of IE but that it may result in overdiagnosis of IE; therefore, these criteria should be applied prospectively to determine their clinical usefulness.

The decline in the lymphoproliferative response to mitogenic stimuli shows marked heterogeneity in elderly individuals. Adequate nutriture is required for optimal immune function, yet nutritional status may be compromised in the elderly. To address whether this variation in the proliferative response of elderly individuals is related to their nutritional status, we studied 61 elderly (80.5 +/- 5.7 year-old) and 27 young (27.3 +/- 3.8 year-old) individuals participating in an ongoing assessment of their immune response to influenza vaccine. Ambulatory elderly individuals were recruited from five different retirement communities and were in good health upon enrollment in the study. Thirty-three percent of young and 54% of elderly subjects reported consuming micronutrient supplements daily during the study. Plasma and peripheral blood mononuclear cells (PBMC) were isolated from fasting individuals twice, 4-6 weeks apart. At both times, proliferative responses to the mitogens phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were significantly lower (P < 0.004) in the elderly compared to the young. However, at both times, elderly participants had plasma concentrations of beta-carotene, retinol, alpha-tocopherol and zinc that were either significantly greater than, or equal to, those of young subjects. No significant correlations between plasma concentrations of beta-carotene, retinol, alpha-tocopherol and zinc and level of proliferative responses to each stimuli were observed in elderly individuals at either time. Thus, the heterogeneity in the proliferative response to mitogenic stimuli exhibited by a healthy elderly population cannot be attributed to differences in these nutritional parameters.

Elderly patients are at high risk for urinary tract infection (UTI). Infections of the urinary tract may be classified as asymptomatic bacteriuria, uncomplicated cystitis, uncomplicated pyelonephritis or complicated UTI. The micro-organisms responsible for causing UTI are largely predictable and dictate therapy when indicated. UTIs may be diagnosed by both nonculture and culture techniques. Asymptomatic bacteriuria, though quite common in the elderly, should rarely be treated. Treatment of symptomatic uncomplicated and complicated UTIs is largely dictated by the known or expected pathogen(s) and classification of the infection. Additional features affecting the treatment of UTI in the elderly include allergies, adverse reactions to therapy, drug interactions and modification for renal insufficiency.

To determine if passive immunization could decrease the incidence or severity of Klebsiella and Pseudomonas aeruginosa infections, patients admitted to intensive care units of 16 Department of Veterans Affairs and Department of Defense hospitals were randomized to receive either 100 mg/kg intravenous hyperimmune globulin (IVIG), derived from donors immunized with a 24-valent Klebsiella capsular polysaccharide plus an 8-valent P. aeruginosa O-polysaccharide-toxin A conjugate vaccine, or an albumin placebo. The overall incidence and severity of vaccine-specific Klebsiella plus Pseudomonas infections were not significantly different between the groups receiving albumin and IVIG. There was some evidence that IVIG may decrease the incidence (2.7% albumin vs. 1.2% IVIG) and severity (1.0% vs. 0.3%) of vaccine-specific Klebsiella infections, but these reductions were not statistically significant. The trial was stopped because it was statistically unlikely that IVIG would be protective against Pseudomonas infections at the dosage being used. Patients receiving IVIG had more adverse reactions (14.4% vs. 9.2%).

There is a high prevalence of bacterial infections in long term care facilities (4.4 to 16.2%). This, together with the fact that antimicrobial resistance is a big concern in current medical practice, makes infection control so important in nursing home care. This article covers the mechanisms of antibacterial resistance and focuses on 4 major antibacterial-resistant bacteria. Vancomycin is the treatment of choice for methicillin-resistant Staphylococcus aureus (MRSA). Colonisation with MRSA is not uncommon in nursing homes and eradication is probably not necessary. Any clinically important enterococcal infection should be tested for high-level resistance. An infectious disease consultation should be sought for vancomycin-resistant enterococcal infections. Gram-negative bacilli have developed multi-resistance. Susceptibility testing can identify the most appropriate therapy. Multiresistance should also be considered when treating Streptococcus pneumoniae. Overall, handwashing is highly recommended. Barrier precautions, minimising hospitalisations and avoiding unnecessary personnel rotation can reduce the chance of resistance spread.

Objective: To determine whether treatment of symptomatic bacteriuria in older ambulatory women affects the subsequent development of symptoms of urinary tract infection., Design: A controlled clinical trial., Participants: Older women not having urinary catheters., Measurements: Urine cultures every 6 months (the same organism at 10(5) colony-forming units or more per mL on two midstream urine specimens defined asymptomatic bacteriuria) and questionnaire surveys for the new development of symptoms of urinary tract infection (dysuria, frequency, urgency, low back pain with fever) 1, 3, and 6 months after the initial survey., Results: Of the 23 initially culture-positive participants receiving antibiotic treatment for symptomatic bacteriuria, nine were culture positive at 6 months, which contrasts with 18 of 27 who received no treatment or placebo, P = .05. However, symptoms of urinary tract infection were more common in the antibiotic-treated group., Conclusion: Antibiotic therapy effectively reduced the subsequent occurrence of positive urine cultures, but symptoms were not reduced. Based on this study of morbidity, previous studies failing to show any relation to mortality, and the cost and complications of antibiotic therapy in the older population, treatment of asymptomatic bacteriuria in older women is contraindicated.