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Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most successful modern pathogens. The same organism that lives as a commensal and is transmitted in both health-care and community settings is also a leading cause of bacteraemia, endocarditis, skin and soft tissue infections, bone and joint infections and hospital-acquired infections. Genetically diverse, the epidemiology of MRSA is primarily characterized by the serial emergence of epidemic strains. Although its incidence has recently declined in some regions, MRSA still poses a formidable clinical threat, with persistently high morbidity and mortality. Successful treatment remains challenging and requires the evaluation of both novel antimicrobials and adjunctive aspects of care, such as infectious disease consultation, echocardiography and source control. In this Review, we provide an overview of basic and clinical MRSA research and summarize the expansive body of literature on the epidemiology, transmission, genetic diversity, evolution, surveillance and treatment of MRSA.Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen both within hospitals and in the community. In this Review, Fowler and colleagues provide an overview of basic and clinical MRSA research and explore the epidemiology, transmission, genetic diversity, evolution, surveillance and treatment of MRSA.

A 3-year trial involving persons with a family history of dementia showed no differences in cognitive change or brain MRI outcomes between the MIND diet, designed for neuroprotection, and a control diet.

AbstractObjectiveTo determine the impact of lifestyle factors on life expectancy lived with and without Alzheimer’s dementia.DesignProspective cohort study.SettingThe Chicago Health and Aging Project, a population based cohort study in the United States.Participants2449 men and women aged 65 years and older.Main exposureA healthy lifestyle score was developed based on five modifiable lifestyle factors: a diet for brain health (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay—MIND diet score in upper 40% of cohort distribution), late life cognitive activities (composite score in upper 40%), moderate or vigorous physical activity (≥150 min/week), no smoking, and light to moderate alcohol consumption (women 1-15 g/day; men 1-30 g/day).Main outcomeLife expectancy with and without Alzheimer’s dementia in women and men.ResultsWomen aged 65 with four or five healthy factors had a life expectancy of 24.2 years (95% confidence interval 22.8 to 25.5) and lived 3.1 years longer than women aged 65 with zero or one healthy factor (life expectancy 21.1 years, 19.5 to 22.4). Of the total life expectancy at age 65, women with four or five healthy factors spent 10.8% (2.6 years, 2.0 to 3.3) of their remaining years with Alzheimer’s dementia, whereas women with zero or one healthy factor spent 19.3% (4.1 years, 3.2 to 5.1) with the disease. Life expectancy for women aged 65 without Alzheimer’s dementia and four or five healthy factors was 21.5 years (20.0 to 22.7), and for those with zero or one healthy factor it was 17.0 years (15.5 to 18.3). Men aged 65 with four or five healthy factors had a total life expectancy of 23.1 years (21.4 to 25.6), which is 5.7 years longer than men aged 65 with zero or one healthy factor (life expectancy 17.4 years, 15.8 to 20.1). Of the total life expectancy at age 65, men with four or five healthy factors spent 6.1% (1.4 years, 0.3 to 2.0) of their remaining years with Alzheimer’s dementia, and those with zero or one healthy factor spent 12.0% (2.1 years, 0.2 to 3.0) with the disease. Life expectancy for men aged 65 without Alzheimer’s dementia and four or five healthy factors was 21.7 years (19.7 to 24.9), and for those with zero or one healthy factor life expectancy was 15.3 years (13.4 to 19.1).ConclusionA healthy lifestyle was associated with a longer life expectancy among men and women, and they lived a larger proportion of their remaining years without Alzheimer’s dementia. The life expectancy estimates might help health professionals, policy makers, and stakeholders to plan future healthcare services, costs, and needs.

A high adherence to the Mediterranean-Dietary Approaches to Stop Hypertension Diet Intervention for Neurodegenerative Delay (MIND) has been associated with better cognition and a lower risk of dementia in some but not all studies. We measured adherence to MIND and its association with cognitive health in the UK Biobank (UKB). A MIND score was derived from 24 h diet recall questionnaires for 120,661 participants who completed at least one of seven self-administered cognitive function tests. In a subset of 78,663 participants aged 55+, diagnosis of dementia was determined by linked hospital and death records. Multivariable regression and Cox proportional hazard ratio (HR) models were used to examine associations of MIND with cognitive ability and incident dementia. Higher adherence to MIND was associated with a small but significant worsening in performance on five of seven cognitive tests (p < 0.002). Associations were strongest among highly educated participants (p < 0.002 for MIND × education interaction). After a mean follow-up time of 10.5 years, 842 participants developed dementia. Overall, MIND adherence was not associated with incident dementia. An inverse association was observed among females (HR = 0.87 per score standard deviation (SD), p = 0.008) but not males (HR = 1.09, p = 0.11) (p = 0.008 for MIND × sex interaction). Similar associations with cognitive ability and dementia were observed for the Alternative Healthy Eating Index-2010 (AHEI-2010) dietary pattern. Associations were not modified by genetic susceptibility. In UKB, the MIND diet was not associated with better cognitive test scores and only with lower dementia risk in women.

Abstract Background Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Methods This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. Results Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). Conclusions Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range. A multicenter prospective study was performed to evaluate the relationship between day 2 vancomycin exposure profiles and outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia. The collective findings suggest that vancomycin dosing should be guided by the area under the curve (AUC) and day 2 AUCs should be maintained between 400 and 515.

Background: Strawberries have been identified to have antioxidant and anti-inflammatory properties that improve neuronal function and cognition, mostly in animal studies. It is unknown if the consumption of strawberries or related bioactives may reduce the risk of Alzheimer’s dementia risk. Material and Methods: The study was conducted in 925 participants, aged 58–98 years of the Rush Memory and Aging Project. Participants were dementia-free at baseline, completed a food frequency questionnaire, and had at least two annual neurological evaluations. The diagnosis of Alzheimer’s dementia was based on structured clinical neurological examination and standardized diagnostic criteria. The association of strawberry intake and incident Alzheimer’s dementia was analyzed using proportional hazard models adjusted for age, sex, education, physical activity, participation in cognitive activities, APOE-ɛ4 genotype, dietary intake of other fruits, and total calorie intake. Results: A total of 245 participants developed Alzheimer’s dementia over the mean follow-up of 6.7 (±3.6) years. Higher strawberry intake was associated with reduced risk of Alzheimer’s dementia (HR = 0.76, 95% CI: 0.60–0.96). In separate adjusted models, highest vs. lowest quartile intakes of Vitamin C (HR = 0.64, 95% CI: 0.45, 0.92), Pelargonidin (0.63, 95% CI: 0.43, 0.92), total anthocyanidins (0.69, 95% CI: 0.48, 0.99), and total flavonoids (0.67, 95% CI: 0.46, 0.98) were each associated with lower Alzheimer’s dementia risk. These associations remained after further adjustment for cardiovascular conditions. Conclusion: Consumption of strawberries and foods rich in vitamin C, pelargonidin, anthocyanidins, and total flavonoids may reduce the risk of Alzheimer’s dementia.

The clinical features of UTI in young children may not localize to the urinary tract and closely resemble other febrile illnesses. In malaria endemic areas, a child presenting with fever is often treated presumptively for malaria without investigation for UTI. Delayed or inadequate treatment of UTI increases the risk of bacteremia and renal scarring in young children and subsequently complications as hypertension and end stage renal disease in adulthood. A cross-sectional study was carried out in a hospital in western Kenya. Inpatients and outpatients 2 months to five years with axillary temperature ≥37.5°C and no antibiotic use in the previous week were enrolled between September 2012 and April 2013. Urine dipstick tests, microscopy, and cultures were done and susceptibility patterns to commonly prescribed antibiotics established. UTI was defined as presence of pyuria (a positive urine dipstick or microscopy test) plus a positive urine culture. A total of 260 subjects were recruited; 45.8% were female and the median age was 25months (IQR: 13, 43.5). The overall prevalence of UTI was 11.9%. Inpatients had a higher prevalence compared to outpatients (17.9% v 7.8%, p = 0.027). UTI co-existed with malaria but the association was not significant (OR 0.80, p = 0.570). The most common organisms isolated were Escherichia coli (64.5%) and Staphylococcus aureus (12.9%) and were sensitive to ciproflaxin, cefuroxime, ceftriaxone, gentamycin and nitrofurantoin but largely resistant to more commonly used antibiotics such as ampicillin (0%), amoxicillin (16.7%), cotrimoxazole (16.7%) and amoxicillin-clavulinate (25%). Our study demonstrates UTI contributes significantly to the burden of febrile illness in young children and often co-exists with other infections. Multi-drug resistant organisms are common therefore choice of antimicrobial therapy should be based on local sensitivity pattern.

Background Staphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15–50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S. aureus bacteremia without the need for durable central venous access. Methods DOTS is a phase 2b, multicenter, randomized, assessor-blinded, superiority, active-controlled, parallel-group trial. The trial will enroll 200 adults diagnosed with complicated S. aureus bacteremia, including definite or possible right-sided infective endocarditis, who have been treated with effective antibiotic therapy for at least 72 h (maximum 10 days) and with subsequent clearance of bacteremia prior to randomization to study treatment. Subjects will be randomized 1:1 to complete their antibiotic treatment course with either two doses of dalbavancin on days 1 and 8, or with a total of 4–8 weeks of standard intravenous antibiotic therapy. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at day 70 for patients randomized to dalbavancin versus standard of care. Key secondary endpoints include quality of life outcomes and pharmacokinetic analyses of dalbavancin. Discussion The DOTS trial will establish whether dalbavancin is superior to standard parenteral antibiotic therapy for the completion of treatment of complicated S. aureus bacteremia. Trial registration US National Institutes of Health ClinicalTrials.gov NCT04775953 . Registered on 1 March 2021

In this trial involving 387 patients with Staphylococcus aureus bacteremia, ceftobiprole, a cephalosporin active against methicillin-sensitive and -resistant S. aureus , was noninferior to daptomycin.