Outcomes with daptomycin versus standard therapy for osteoarticular infections associated with Staphylococcus aureus bacteraemia.

OBJECTIVES: To evaluate the clinical characteristics, treatment and outcomes of patients with osteoarticular infections (OAIs) associated with Staphylococcus aureus bacteraemia (SAB). METHODS: The clinical characteristics and outcomes for patients with OAI were described using a post hoc analysis of an open label, randomized trial comparing daptomycin with standard therapy (vancomycin or anti-staphylococcal penicillin with initial gentamicin) for the treatment of SAB. RESULTS: OAI occurred in 32 of 121 patients (21 daptomycin and 11 standard therapy) with complicated SAB (18 septic arthritis, 9 vertebral osteomyelitis and 7 others). Two patients had osteomyelitis in more than one site. Success rates seen in two groups were as follows: vertebral osteomyelitis [3/5 (60%) daptomycin versus 0/2 (0%) comparator], septic arthritis [7/11 (64%) versus 3/5 (60%)], sternal osteomyelitis [3/3 (100%) versus 1/2 (50%)] and long bone osteomyelitis [0/1 (0%) versus 1/1 (100%)]. Success rates in both treatment groups improved with surgical therapy. Creatine phosphokinase elevations to >500 IU/L occurred in one patient on daptomycin who discontinued therapy, whereas renal impairment developed in three patients on standard therapy, two of whom discontinued therapy. Two patients treated with daptomycin and one patient on vancomycin had increases in S. aureus MICs to daptomycin and vancomycin, respectively. Three patients treated with daptomycin died following completion of therapy, with mortality attributed to multiple co-morbid conditions and inadequate debridement of OAIs in these patients. No deaths were reported in the standard therapy group. CONCLUSIONS: Daptomycin may be considered an alternative to standard therapy in the treatment of patients with complicated SAB and OAI.

Prosthetic valve endocarditis due to coagulase-negative staphylococci: findings from the International Collaboration on Endocarditis Merged Database.

Infective endocarditis due to coagulase-negative staphylococci is increasingly recognized as a difficult-to-treat disease associated with poor outcome. The aim of this report is to describe the characteristics and outcome of patients with prosthetic valve endocarditis (PVE) due to coagulase-negative staphylococci versus those of patients with PVE due to Staphylococcus aureus and viridans streptococci. Patients were identified through the International Collaboration on Endocarditis Merged Database. A total of 54 cases of coagulase-negative staphylococci PVE, 58 cases of S. aureus PVE, and 63 cases of viridans-streptococci-related PVE were available for analysis. There was no difference between the three groups with respect to the type of valve involved or the rate of embolization. However, heart failure was encountered more frequently with coagulase-negative staphylococci (54%) than with either S. aureus (33%; p=0.03) or viridans streptococci (32%; p=0.02). In addition, valvular abscesses complicated 39% of infections due to coagulase-negative staphylococci compared with 22% of those due to S. aureus (p=0.06) and 6% of those due to viridans streptococci (p<0.001). Mortality was highest in patients with S. aureus and coagulase-negative staphylococcal endocarditis (47 and 36%, respectively; p=0.22) and was considerably lower in patients with viridans streptococcal endocarditis (p=0.002 compared to patients with coagulase-negative staphylococcal endocarditis). The results of this analysis demonstrate the aggressive nature of coagulase-negative staphylococcal PVE and the substantially greater morbidity and mortality associated with this infection compared to PVE caused by other pathogens.

Enterococcal prosthetic valve infective endocarditis: report of 45 episodes from the International Collaboration on Endocarditis-merged database.

Enterococcal prosthetic valve infective endocarditis (PVE) is an incompletely understood disease. In the present study, patients with enterococcal PVE were compared to patients with enterococcal native valve endocarditis (NVE) and other types of PVE to determine differences in basic clinical characteristics and outcomes using a large multicenter, international database of patients with definite endocarditis. Forty-five of 159 (29%) cases of definite enterococcal endocarditis were PVE. Patients with enterococcal PVE were demographically similar to patients with enterococcal NVE but had more intracardiac abscesses (20% vs. 6%; p=0.009), fewer valve vegetations (51% vs. 79%; p<0.001), and fewer cases of new valvular regurgitation (12% vs. 45%; p=0.01). Patients with either enterococcal PVE or NVE were elderly (median age, 73 vs. 69; p=0.06). Rates of in-hospital mortality, surgical intervention, heart failure, peripheral embolization, and stroke were similar in both groups. Patients with enterococcal PVE were also demographically similar to patients with other types of PVE, but mortality may be lower (14% vs. 26%; p=0.08). Notably, 93% of patients with enterococcal PVE came from European centers, as compared with only 79% of patients with enterococcal NVE (p=0.03). Thus, patients with enterococcal PVE have higher rates of myocardial abscess formation and lower rates of new regurgitation compared to patients with enterococcal NVE, but there are no differences between the groups with regard to surgical or mortality rates. In contrast, though patients with enterococcal PVE and patients with other types of PVE share similar characteristics, mortality is higher in the latter group. Importantly, the prevalence of enterococcal PVE was higher in the European centers in this study.

Enterococcal endocarditis: 107 cases from the international collaboration on endocarditis merged database.

PURPOSE: To describe clinical features and outcomes of enterococcal left-sided native valve endocarditis and to compare it to endocarditis caused by other pathogens. SUBJECTS AND METHODS: Patients in the International Collaboration on Endocarditis-Merged Database were included if they had left-sided native valve endocarditis. Demographic characteristics, clinical features, and outcomes were analyzed. Multivariable analysis evaluated enterococcus as a predictor of mortality. RESULTS: Of 1285 patients with left-sided native valve endocarditis, 107 had enterococcal endocarditis. Enterococcal endocarditis was most frequently seen in elderly men, frequently involved the aortic valve, tended to produce heart failure rather than embolic events, and had relatively low short-term mortality. Compared to patients with non-enterococcal endocarditis, patients with enterococcal endocarditis had similar rates of nosocomial acquisition, heart failure, embolization, surgery, and mortality. Compared to patients with streptococcal endocarditis, patients with enterococcal endocarditis were more likely to be nosocomially acquired (9 of 59 [15%] vs 2 of 400 [1%]; P <.0001) and have heart failure (49 of 107 [46%] vs 234 of 666 [35%]; P = 0.03). Compared to patients with S. aureus endocarditis, patients with enterococcal endocarditis were less likely to embolize (28 of 107 [26%] vs 155 of 314 [49%]; P <.0001) and less likely to die (12 of 107 [11%] vs 83 of 313 [27%]; P = 0.001). Multivariable analysis of all patients with left-sided native valve endocarditis showed that enterococcal endocarditis was associated with lower mortality (odds ratio [OR] 0.49; 95% confidence interval [CI] 0.24 to 0.97). CONCLUSIONS: Enterococcal native valve endocarditis has a distinctive clinical picture with a good prognosis.

Emergence of endocarditis due to group D streptococci: findings derived from the merged database of the International Collaboration on Endocarditis.

The aim of the present study was to compare the epidemiological and clinical characteristics of Streptococcus bovis endocarditis with those of endocarditis caused by oral streptococci, using data obtained from a large international database of uniformly defined cases of infective endocarditis. S. bovis, a well-known cause of infective endocarditis, remains the common name used to designate group D nonenterococcal streptococci. In some countries, the frequency of S. bovis endocarditis has increased significantly in recent years. Data from the International Collaboration on Endocarditis merged database was used to identify the main characteristics of S. bovis endocarditis and compared them with those of infective endocarditis (IE) due to oral streptococci. The database contained 136 cases of S. bovis IE and 511 cases of IE due to oral streptococci. Patients with S. bovis IE were significantly older those with IE due to oral streptococci (63+/-16 vs. 55+/-18 years, P<0.00001). The proportion of streptococcal IE due to S. bovis increased from 10.9% before 1989 to 23.3% after 1989 (P=0.0007) and was 56.7% in France as compared with 9.4% in the rest of Europe and 6.0% in the USA (P<0.00001). Patients with S. bovis IE had more comorbidity and never used intravenous drugs. Complication rates, rates of valve replacement, and mortality rates were similar in the two groups. In conclusion, this study confirmed that S. bovis IE has unique characteristics when compared to endocarditis due to oral streptococci and that it emerged in the 1990s, mainly in France, a finding that is yet unexplained.

Prognostic factors in 61 cases of Staphylococcus aureus prosthetic valve infective endocarditis from the International Collaboration on Endocarditis merged database.

Staphylococcus aureus prosthetic valve infective endocarditis (SA-PVIE) is associated with a high mortality rate, but prognostic factors have not been clearly elucidated. The International Collaboration on Endocarditis merged database (ICE-MD) contained 2212 cases of definite infective endocarditis (as defined using the Duke criteria), 61 of which were SA-PVIE. Overall mortality rate was 47.5%, stroke was associated with an increased risk of death, and early valve replacement was not associated with a significant survival benefit in the whole population; however, patients who developed cardiac complications and underwent early valve replacement had the lowest mortality rate (28.6%).

Characterization of antibody responses to annual influenza vaccination over four years in a healthy elderly population.

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.

Immune response to influenza vaccine in healthy elderly: lack of association with plasma beta-carotene, retinol, alpha-tocopherol, or zinc.

Immunity and nutritional status are compromised with age, yet the relationship between them is unclear. Immune responses and plasma micronutrient levels of 61 healthy elderly (mean 81 years) and 27 young (mean 27 years) were assessed before and after immunization with trivalent influenza vaccine (FLU). FLU-induced proliferation and IFN-gamma levels of elderly were lower than young before and after immunization. Proliferation and IFN-gamma levels increased after immunization of young, but not elderly. FLU-induced IL-6 and IL-10 levels did not change after immunization of either group. While antibody titers to all three FLU components increased after vaccination of young and elderly, post-vaccination titers of elderly were lower than young. Although plasma retinol and zinc levels of young and elderly were similar before and after vaccination, elderly had higher plasma beta-carotene and alpha-tocopherol levels at both assessments that increased after vaccination. Importantly, plasma micronutrient levels were comparable for elderly with or without intact (titers >/=40 and fourfold rise post-vaccination) antibody responses after vaccination. These results suggest that differences in these plasma micronutrients (1) are not required to observe decreased FLU responses of healthy elderly compared to young and (2) are not associated with differences in antibody responses among healthy elderly.

Pathogens resistant to antimicrobial agents. Epidemiology, molecular mechanisms, and clinical management.

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.

Risk factors for infective endocarditis: oral hygiene and nondental exposures.

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.

Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA).

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.

Immune response to influenza vaccination in a large healthy elderly population.

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.

Infective Endocarditis: Current Guidelines on Prophylaxis.

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.

Dental and cardiac risk factors for infective endocarditis. A population-based, case-control study.

BACKGROUND: Although antibiotic prophylaxis against infective endocarditis is recommended, the true risk factors for infective endocarditis are unclear. OBJECTIVE: To quantitate the risk for endocarditis from dental treatment and cardiac abnormalities. DESIGN: Population-based, case-control study. SETTING: 54 hospitals in the Philadelphia area. PATIENTS: Persons with community-acquired infective endocarditis not associated with intravenous drug use were compared with community residents, matched by age, sex, and neighborhood of residence. MEASUREMENTS: Information on demographic characteristics, host risk factors, and dental treatment was obtained from structured telephone interviews, dental records, and medical records. RESULTS: During the preceding 3 months, dental treatment was no more frequent among case-patients than controls (adjusted odds ratio, 0.8 [95% CI, 0.4 to 1.5]). Of 273 case-patients, 104 (38%) knew of previous cardiac lesions compared with 17 controls (6%) (adjusted odds ratio, 16.7 [CI, 7.4 to 37.4]). Case-patients more often had a history of mitral valve prolapse (adjusted odds ratio, 19.4 [CI, 6.4 to 58.4]), congenital heart disease (adjusted odds ratio, 6.7 [CI, 2.3 to 19.4]), cardiac valvular surgery (adjusted odds ratio, 74.6 [CI, 12.5 to 447]), rheumatic fever (adjusted odds ratio, 13.4 [CI, 4.5 to 39.5]), and heart murmur without other known cardiac abnormalities (adjusted odds ratio, 4.2 [CI, 2.0 to 8.9]). Among case-patients with known cardiac lesions--the target of prophylaxis--dental therapy was significantly (P = 0.03) less common than among controls (adjusted odds ratio, 0.2 [CI, 0.04 to 0.7] over 3 months). Few participants received prophylactic antibiotics. CONCLUSIONS: Dental treatment does not seem to be a risk factor for infective endocarditis, even in patients with valvular abnormalities, but cardiac valvular abnormalities are strong risk factors. Few cases of infective endocarditis would be preventable with antibiotic prophylaxis, even with 100% effectiveness assumed. Current policies for prophylaxis should be reconsidered.

Cytokine production after influenza vaccination in a healthy elderly population.

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 in older adults.

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.

An assessment of the usefulness of the Duke criteria for diagnosing active infective endocarditis.

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 age-associated decline in immune function of healthy individuals is not related to changes in plasma concentrations of beta-carotene, retinol, alpha-tocopherol or zinc.

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.