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.

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.

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.

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%).

Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: an 18-month prospective follow-up.

Our objective was to determine the prevalence and incidence of human immunodeficiency virus (HIV) infection and related risk behaviors among opiate-abusing intravenous drug users (IVDUs) either in or out of methadone treatment. The subjects, 152 in-treatment and 103 out-of-treatment intravenous opiate users, were followed prospectively for 18 months. Behavioral and serologic assessments were made at 6-month intervals, with complete information available on 89% of the sample. Subjects were recruited from a single methadone maintenance program and the surrounding neighborhood in north-central Philadelphia. At baseline, the HIV seroprevalence rate for the total sample was 12%: 10% for the methadone-maintained group and 16% for the out-of-treatment group. Out-of-treatment subjects were injecting drugs, sharing needles, visiting shooting galleries, and practicing unsafe sex at significantly higher rates than in-treatment subjects. Follow-up of HIV-negative subjects over the next 18 months showed conversion rates of 3.5% for those who remained in methadone maintenance versus 22% for those who remained out of treatment. The sixfold difference in rate of seroconversion between the two groups suggests that although rapid transmission of HIV still occurs, opiate-abusing IVDUs who enter methadone treatment are significantly less likely to become infected. In contrast, those opiate addicts who do not enter treatment are at significantly higher risk of contracting and spreading the disease. Implications for developing additional risk interventions for out-of-treatment IVDUs are discussed.

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.

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.

Disseminated actinomycosis with spinal cord compression: report of two cases.

We studied two patients with vertebral actinomycosis and symptoms of spinal cord compression. Both patients had a chronic illness characterized by multiple draining skin lesions, weight loss, and progressive leg weakness. They responded to antibiotic therapy and corticosteroids without neurosurgical intervention. The patients were treated with antibiotics for 12 months, and remained well, without major neurologic disorder, for 2 years after stopping medication.

Lack of association between bacteriuria and symptoms in the elderly.

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.

Epidemiology of bacteriuria in an elderly ambulatory population.

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.

Assessing diagnostic criteria for active infective endocarditis.

A study was performed to describe agreement among experts on their classification of patients, in the absence of information concerning risk factors, as to the presence of infective endocarditis (IE). The study also assessed the clinical characteristics that enabled the experts to determine that a patient had IE. All patients with a discharge diagnosis of IE were identified prospectively from 54 hospitals in the Delaware Valley over a 3-year period. Patients were part of a case-control study of risk factors for IE. Three infectious disease experts independently reviewed abstracted hospital records and classified each of 151 eligible patients as a definite, probable or possible case, or a probable noncase, both based on clinical judgement and using a modified standard definition. Experts were more likely to classify a patient as a definite case of IE on the basis of clinical judgement than by using the modified standard definition. Agreement between reviewers was 92 to 95% when they were distinguishing only probable non-cases from others. Agreement between reviewers on specific categories was lower (40 to 58%). The number of positive blood cultures was a strong predictor of a patient's being classified as a case, as was the type of infecting organism. It is concluded that experts are willing to make a definitive diagnosis of IE on the basis of blood culture information alone. Further supporting evidence, such as the presence of vegetation on an echocardiogram, is needed when blood culture results are ambiguous.

Incidence of infective endocarditis in the Delaware Valley, 1988-1990.

This population-based study aimed to determine the incidence of native, prosthetic, and bioprosthetic valve nosocomial infective endocarditis (IE), and IE associated with the use of injected drugs. Patients with IE during 27 months over the years 1988 to 1990, and residing in any of 6 counties in the Philadelphia metropolitan area were identified. An expert panel reviewed all patients to verify the diagnosis. Incidence rates were estimated after adjustment for failure to recruit and underreporting. Of 853 potential patients, 670 (79%) met the inclusion criteria. The overall incidence rate of IE was 11.6 cases/100,000 person-years (95% confidence interval [CI] 10.8 to 12.4). The rates for specific types of IE were: 4.45 (95% CI 3.97 to 4.94) for community-acquired native valve, 0.94 (95% CI 0.72 to 1.12) for prosthetic valve, 0.94 (95% CI 0.71 to 1.16) for nosocomial, and 5.34 (95% CI 4.80 to 5.87) for IE associated with use of injected drugs. Previous population studies found overall incidence rates of 1.7 to 4 cases/100,000 person-years, similar to our rate for community-acquired native valve IE. Type-specific rates have not been previously reported. The higher overall rate in this study is partly related to the high prevalence of injection drug use in our area.

Developing policies and guidelines.

Practice guidelines are proliferating in the era of managed care. Hospital epidemiologists frequently are asked to author guidelines of infection control. The greatest challenge in the process is not writing the guidelines but implementing them. This article offers practical advice on which topic to select and on how to develop and implement guidelines.

Epidemiology of asymptomatic bacteriuria in elderly women.

We studied asymptomatic bacteriuria in elderly ambulatory women residents without indwelling catheters in self-contained apartment houses at the Philadelphia Geriatric Center (PGC), in the nursing home at PGC, and in several life-care communities (LCC). Subjects were studied every 6 months from January 1983 through January 1989, and since enrollment was continuous some participated in more surveys than others. PGC residents were middle class and lived either in a self care apartment house (CL) or nursing home (NH); LCC residents were middle or upper class. Antimicrobial therapy for asymptomatic bacteriuria was not given by the study team. The ages of the 865 women studied averaged 80.3, 82.8, and 83.3 years in LCC, CL, and NH, respectively. On each survey about 11% at LCC, 18% at CL, and 25% at NH sites had positive cultures. Turnover was high. The conversion rate from a negative to a positive culture was 5% at LCC, 11% at CL, and 8% at NH. The reversion rate from a positive to a negative culture was 33% at LCC, 34% at CL and 31% at NH (P greater than 0.05). Persistent infection with the same organism was uncommon. Infection risk was associated with residence, which was partially explained by a factor evaluating mobility, but was unrelated to age or scores evaluating activities of daily living or mental status. Besides mobility, other more complex factors play a role in the acquisition of infection.

Does treatment of asymptomatic bacteriuria in older ambulatory women reduce subsequent symptoms of urinary tract infection?

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.

New uses for old drugs.

Existing therapies are often tried when new diseases are discovered or new manifestations of known organisms are recognized. This article reviews the successful application of older commonly used antibiotics to several representative "new" or "newly recognized" illnesses. Examples include new uses for the antistaphylococcal agents, penicillin, the tetracyclines, erythromycin, vancomycin, trimethoprim-sulfamethoxazole, pyrazinamide, metronidazole, clindamycin, and others.

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

The emergence of resistance to antimicrobial agents continues to be a major problem among both nosocomial and community-acquired pathogens. Bacteria employ a variety of strategies to avoid the inhibitory effects of antibiotic agents, and have evolved highly efficient means for the dissemination of resistance traits. The result has been the emergence of multidrug-resistant pathogens such as penicillin-resistant pneumococci, vancomycin-resistant enterococci, methicillin-resistant staphylococci, as well as a variety of multiresistant gram-negative organisms. Control of antibiotic-resistant pathogens will provide a major challenge for both the medical community and society in general. The implication of a failure to meet this challenge is the eventual arrival of the "post antibiotic era."

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.

Pseudo-outbreak of Bacillus species: related to fibreoptic bronchoscopy.

In July and August 1980, Bacillus spp. were isolated with unusual frequency from bronchial washings obtained during bronchoscopy performed with fibreoptic equipment. Clinical disease in culture-positive patients was not apparent; but Bacillus spp. were recovered from one component of the bronchoscope, the automatic suction valve. It appeared that secretions became contaminated during passage through the valve en route to a collection device. After institution of controls directed primarily at proper storage and maintenance, the number of isolations of Bacillus spp. decreased significantly. Thus, investigation revealed a site for contamination not previously described and the results suggest that in future outbreaks, cultures of the component parts may permit localization of the site of contamination which may help focus control measures.

Urinary tract infection: economic considerations.

Urinary tract infection results in significant morbidity and mortality while consuming large amounts of national resources. The prevention, diagnosis, and treatment of urinary tract infection produce both costs and benefits, and economic analysis provides a rational framework for looking at these effects. The goals and methods of economic analysis in medicine are summarized, and strategies to address uncomplicated cystitis, nosocomial urinary tract infection, and pyelonephritis are reviewed, with an emphasis on the economic trade-offs faced by decision makers.