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Background. Because of its ease of dosing, vancomycin is commonly used to treat methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in patients undergoing long-term hemodialysis. Clinical outcomes resulting from such a therapeutic strategy have not been well defined. Methods. We prospectively identified patients undergoing long-term hemodialysis who received a diagnosis of MSSA bacteremia. Clinical outcomes were grouped according to the predominant antibiotic received during their therapy (vancomycin or a first-generation cephalosporin [cefazolin]). Treatment failure (defined as death or recurrent infection) was determined at 12 weeks after the initial positive blood culture results. A multivariable analysis was used to adjust for confounders. Results. During an 84-month period, 123 hemodialysis-dependent patients with MSSA bacteremia were identified. Patients receiving vancomycin (n = 77) tended to be younger (51 vs. 57 years; P = .06) and had a lower rates of metastatic complications at presentation (11.7% vs. 36.7%; P = .001) than did those receiving cefazolin (n = 46). The 2 groups were similar with regard to Acute Physiology and Chronic Health Evaluation II scores, comorbidities, source of infection, type of hemodialysis access, and access removal rates. Treatment failure was more common among patients receiving vancomycin (31.2% vs. 13%; P = .02). In the multivariable analysis, factors independently associated with treatment failure included vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15–13.45) and retention of the hemodialysis access (odds ratio, 4.99; 95% confidence interval, 1.89–13.76). Conclusions. Hemodialysis-dependent patients with MSSA bacteremia treated with vancomycin are at a higher risk of experiencing treatment failure than are those receiving cefazolin. In the absence of patient specific circumstances (e.g., allergy to β-lactams), vancomycin should not be continued beyond empirical therapy for hemodialysis-dependent patients with MSSA bacteremia.

Although cardiac devices have been found to reduce symptoms and mortality rates in appropriate patient populations, the implications of certain important risks, such as infection, are incompletely understood. The purpose of this study was to use a large population-based database to define the population that is at risk for cardiac device infections, determine the prevalence of device infections, and study changes in the rates of cardiac device implantation and infection in the past decade. Patients with cardiac device implantations and infections were identified with claims files from the Health Care Finance Administration for Medicare beneficiaries from January 1, 1990, through December 31, 1999. Rates of implantation of cardiac devices were determined. Time trend analyses were performed to determine the significance of the observed change in rates. Cardiac device implantation rates increased from 3.26 implantations per 1000 beneficiaries in 1990 to 4.64 implantations per 1000 beneficiaries in 1999, which represents an increase of 42% in 10 years ( P for trend <.001). Cardiac device infections showed a larger increase, from 0.94 device infections per 1000 beneficiaries in 1990 to 2.11 device infections per 1000 beneficiaries in 1999, which represents an increase of 124% during the study period ( P for trend <.001). During the previous decade, there was a significant increase in both cardiac device implantations and infections in elderly patients, although the increase in the rates of device infections was substantially higher. Additional studies are needed to better understand the relationship and timing between cardiac device implantation and infection.

Background: Infective endocarditis (IE) has increased markedly among people who inject drugs (PWID). Harm reduction is a tool to help PWID improve health outcomes and mitigate IE. Objectives: To understand the knowledge, perceptions, past engagement, and planned use of harm reduction services from syringe services programs (SSPs) for PWID hospitalized with IE. Design: Qualitative study of PWID hospitalized with IE. Methods: The research team conducted semi-structured interviews with 16 participants at a large academic hospital from June 2021 to May 2022. Two study personnel coded the interviews and analyzed the data using a combination of structural codes, applied thematic analysis, and thematic comparison. Results: The majority of participants reported past experiences obtaining safe injection supplies from SSPs, and participants generally viewed SSPs as places for facilitating safer injecting practices, receiving sterile supplies, learning about harm reduction, and/or obtaining overdose reversal kits. However, some participants reported being unable to access SSPs because of their rurality, lack of SSP availability, or transportation barriers. In addition, some participants reported a lack of interest in receiving SSP information during hospitalization, believing that it would enable an undesired return to drug use, while others felt that SSP services would not be relevant for them post-hospitalization. Conclusion: Patient past and planned use of harm reduction services offered by SSPs was impacted by geographic barriers to accessibility and patient concerns that SSPs would facilitate an undesired return to drug use. Health systems have an opportunity to improve patient usage of harm reduction services post-hospitalization by improving patient education and integrating harm reduction services as tools of care.

Rural areas comprise complex social and ecological systems that are nested in sub-systems at higher spatial and governance levels. At times, influence from higher level (sub) systems may threaten the integrity of local communities. Commoning designed and implemented across levels can address such challenges. A rural village is utilised to extend understandings of how commoning can be structured to tackle these challenges in the revitalisation process. This paper analyses how agricultural commoning at the village level can become nested with the wider system to restore the sub-systems integrity. This aids the identification of favourable designs of commoning and provides alternative ways to address challenges rural areas face.

Background Telavancin, a novel lipoglycopeptide, exerts concentration-dependent, rapid bactericidal activity on account of its multiple mechanisms of action. Telavancin is highly active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate, and vancomycin-resistant strains. Methods We conducted a randomized, double-blind, controlled, phase-2 clinical trial. Patients ⩾18 years of age with a diagnosis of complicated skin and soft-tissue infection caused by suspected or confirmed gram-positive organisms were randomized to receive either intravenously administered telavancin once daily or standard therapy (antistaphylococcal penicillin 4 times daily or vancomycin twice daily). Results For the study, 167 patients were randomized and received at least 1 dose of study medication. Success rates were similar in all analysis populations at the test-of-cure evaluation. Of patients with S. aureus infection at baseline (n = 102), 80% of the telavancin group were cured and 77% of the standard therapy group were cured. For patients with MRSA infection at baseline (n = 48), cure rates were 82% for the telavancin group and 69% for the standard therapy group. Microbiologic eradication in patients with MRSA infection was 84% for the telavancin group versus 74% for the standard therapy group. MIC90 values were lower for telavancin in all tested strains of S. aureus (⩽0.25 ug/mL) compared with the MIC90 values for vancomycin and oxacillin. Similar proportions of patients discontinued therapy for adverse events in both treatment groups (∼5%). Fewer serious adverse events were reported in the telavancin group (4 events) than were for the standard therapy group (9). Conclusion Clinical and microbiological results of this study support the further development of telavancin, especially for treatment of infection due to MRSA.

Repeat infective endocarditis due to the same species can represent relapse of the initial infection or a new infection. We used time-based clinical criteria and pulsed-field gel electrophoresis-based molecular criteria to classify 13 cases of repeat infective endocarditis as either relapse or reinfection. The agreement between clinical and molecular criteria was imperfect (agreement in 10 [77%] of 13 cases).

Background Hospitalizations for infective endocarditis (IE) associated with opioid use disorder (O-IE) have increased in the USA and have been linked to high rates of discharge against medical advice (DAMA). DAMA represents a truncation of care for a severe infection, yet patient outcomes after DAMA are unknown. Objective This study aimed to assess readmissions following O-IE and quantify the impact of DAMA on outcomes. Design A retrospective study of a nationally representative dataset of persons’ inpatient discharges in the USA in 2016 Participants A total of 6018 weighted persons were discharged for O-IE, stratified by DAMA vs. other discharge statuses. Of these, 1331 (22%) were DAMA. Main Measures The primary outcome of interest was 30-day readmission rates, stratified by discharge type. We also examined the total number of hospitalizations during the year and estimated the effect of DAMA on readmission. Key Results Compared with non-DAMA, those experiencing DAMA were more commonly female, resided in metropolitan areas, lower income, and uninsured. Crude 30-day readmission following DAMA was 50%, compared with 21% for other discharge types. DAMA was strongly associated with readmission in an adjusted logistic regression model (OR 3.72, CI 3.02–4.60). Persons experiencing DAMA more commonly had ≥2 more hospitalizations during the period (31% vs. 18%, p <0.01), and were less frequently readmitted at the same hospital (49% vs 64%, p <0.01). Conclusions DAMA occurs in nearly a quarter of patients hospitalized for O-IE and is strongly associated with short-term readmission. Interventions to address the root causes of premature discharges will enhance O-IE care, reduce hospitalizations and improve outcomes.

In patients with active infective endocarditis (IE), the relationship between timing of surgery and survival is uncertain. The objective was to evaluate clinical characteristics associated with timing of surgery and the association between surgical timing and 6-month survival in complicated, left-sided IE. In a prospective, multicenter, observational registry (The International Collaboration on Endocarditis-PLUS, registry from 2008 to 2012), clinical factors associated with timing of surgery during the index hospitalization were determined among 485 adult patients with definite, complicated, left-sided IE who underwent cardiac surgery during their index hospitalization. The relationship between early surgical intervention (<7 days from admission to surgery center) and outcome after surgery was analyzed. The primary end point of the study was 6-month survival. The median time to surgery from admission to surgical center was 7 (interquartile range 2-15) days. Patients who underwent earlier surgery were more likely transferred to the surgical center (74.2% vs 46.4%, P < .001) and had a lower percentage of preexisting heart failure (before IE diagnosis) (6.0% vs 17.3%, P < .001) but higher rate of acute heart failure (53.2% vs 38.4%, P = .001). Variables independently associated with surgery <7 days from admission were patient transfer, acute heart failure, and nonelective surgical status (C-index = 0.84), but predicted operative risk was not. Cox proportional hazards modeling with inverse probability of treatment weighting found that earlier surgery was associated with a trend toward higher 6-month mortality compared with later surgery (hazard ratio = 1.68, 95% CI 0.97-2.96; P = .065), particularly surgery within 2 days of admission or transfer. Mortality was significantly associated with operative risk and complicated IE, including Staphylococcus aureus infection and presence of abscess. Earlier surgery in IE is strongly associated with acute heart failure and surgical urgency. After adjustment for operative risk and IE complications, earlier surgery <7 days from admission was associated with a trend toward higher 6-month overall mortality compared with surgery later in the index hospitalization.

Background. Using multinational collections of methicillin-susceptible Staphylococcus aureus (MSSA) isolates from infective endocarditis (IE) and soft tissue infections (STIs), we sought to (1) validate the finding that S. aureus in clonal complex (CC) 30 is associated with hematogenous complications and (2) test the hypothesis that specific genetic characteristics in S. aureus are associated with infection severity. Methods. IE and STI isolates from 2 cohorts were frequency matched by geographic origin. Isolates underwent spa typing to infer CC and multiplex polymerase chain reaction for presence of virulence genes. Results. 114 isolate pairs were genotyped. IE isolates were more likely to be CC30 (19.5% vs 6.2%; P = .005) and to contain 3 adhesins (clfB, cna, map/eap; P < .0001 for all) and 5 enterotoxins (tst, sea, sed, see, and sei; P ≤ .005 for all). CC30 isolates were more likely to contain cna, tst, sea, see, seg, and chp (P <.05 for all). Conclusions. MSSA IE isolates were significantly more likely to be CC30 and to possess a distinct repertoire of virulence genes than MSSA STI isolates from the same region. The genetic basis of this association requires further study.

Background Ertapenem is a once-daily broad spectrum carbapenem that is increasingly used to treat polymicrobial osteomyelitis due to diabetic foot and traumatic wound infections. However, limited data exists on ertapenem use for osteomyelitis. This study aimed to characterize outcomes and adverse effects with empiric use of ertapenem for osteomyelitis. Findings A total of 112 patients presenting to Duke, Durham Regional or Durham VA Medical Centers with a suspected diagnosis of osteomyelitis and ertapenem use from 11/2001 to 8/2009 were screened, and 12 subjects met inclusion criteria for the study. Mean age was 60 ± 16 years, 68% were female, 75% were Caucasian, and the most common comorbidities included diabetes (58%), peripheral vascular disease (42%), and history of tobacco use (75%). Over half of the patients presented to a primary care clinic or emergency room greater than six months after the onset of clinical symptoms. Bone culture was obtained for diagnostic guidance in only two cases; and surgical intervention was pursued in three cases. Patients received a mean duration of 34.6 ± 7.8 days of therapy, and in three cases, subsequent suppressive oral antibiotics were given. Six (50%) patients met criteria for clinical success, defined as resolution of clinical signs and symptoms of infection such that discontinuation of antibiotics was deemed appropriate at end of ertapenem therapy, without recurrence at one year follow-up. No adverse drug effects were noted. Conclusions In this case series of mostly community-acquired, lower extremity osteomyelitis, bone biopsy was infrequent, and an average six-week course of empiric ertapenem was well-tolerated with curative rates of 50% at one year.