The Utility of Risk Factors to Define Complicated Staphylococcus aureus Bacteremia in a Setting With Low Methicillin-Resistant S. aureus Prevalence.

INTRODUCTION: Recommended duration of antibiotic treatment of Staphylococcus aureus bacteremia (SAB) is frequently based on distinguishing uncomplicated and complicated SAB, and several risk factors at the onset of infection have been proposed to define complicated SAB. Predictive values of risk factors for complicated SAB have not been validated, and consequences of their use on antibiotic prescriptions are unknown. METHODS: In a prospective cohort, patients with SAB were categorized as complicated or uncomplicated through adjudication (reference definition). Associations and predictive values of 9 risk factors were determined, compared with the reference definition, as was accuracy of Infectious Diseases Society of America (IDSA) criteria that include 4 risk factors, and the projected consequences of applying IDSA criteria on antibiotic use. RESULTS: Among 490 patients, 296 (60%) had complicated SAB. In multivariable analysis, persistent bacteremia (odds ratio [OR], 6.8; 95% confidence interval [CI], 3.9-12.0), community acquisition of SAB (OR, 2.9; 95% CI, 1.9-4.7) and presence of prosthetic material (OR, 2.3; 95% CI, 1.5-3.6) were associated with complicated SAB. Presence of any of the 4 risk factors in the IDSA definition of complicated SAB had a positive predictive value of 70.9% (95% CI, 65.5-75.9) and a negative predictive value of 57.5% (95% CI, 49.1-64.8). Compared with the reference, IDSA criteria yielded 24 (5%) false-negative and 90 (18%) false-positive classifications of complicated SAB. Median duration of antibiotic treatment of these 90 patients was 16 days (interquartile range, 14-19), all with favorable clinical outcome. CONCLUSIONS: Risk factors have low to moderate predictive value to identify complicated SAB and their use may lead to unnecessary prolonged antibiotic use.

[Scaling up Outpatient Parenteral Antimicrobial Therapy (OPAT) service in the Netherlands]. / Thuisbehandeling met intraveneuze antibiotica.

Treatment of infections with intravenous antibiotics does not always require hospital care; specialized home care nurses can administer parenteral treatment at home. Dedicated Outpatient Parenteral Antimicrobial Therapy (OPAT) teams are emerging in an increasing number of hospitals in the Netherlands to supervise treatment selection and provide safety monitoring for patients with home treatment. This specialized, nurse driven team facilitates home treatment by collaborating with infectious disease specialists, pharmacy and home care teams, as well as the patient and treating physician. Demand for OPAT treatment is increasing, but currently a structural financial endorsement is lacking in the Netherlands. A solid financial structure will be essential to ensure safe and effective parenteral antimicrobial therapy at home, which can relieve the strain on hospital care.

Immunogenicity of the mRNA-1273 COVID-19 vaccine in adult patients with inborn errors of immunity.

BACKGROUND: Patients with inborn errors of immunity (IEI) are at increased risk of severe coronavirus disease-2019 (COVID-19). Effective vaccination against COVID-19 is therefore of great importance in this group, but little is known about the immunogenicity of COVID-19 vaccines in these patients. OBJECTIVES: We sought to study humoral and cellular immune responses after mRNA-1273 COVID-19 vaccination in adult patients with IEI. METHODS: In a prospective, controlled, multicenter study, 505 patients with IEI (common variable immunodeficiency [CVID], isolated or undefined antibody deficiencies, X-linked agammaglobulinemia, combined B- and T-cell immunodeficiency, phagocyte defects) and 192 controls were included. All participants received 2 doses of the mRNA-1273 COVID-19 vaccine. Levels of severe acute respiratory syndrome coronavirus-2-specific binding antibodies, neutralizing antibodies, and T-cell responses were assessed at baseline, 28 days after first vaccination, and 28 days after second vaccination. RESULTS: Seroconversion rates in patients with clinically mild antibody deficiencies and phagocyte defects were similar to those in healthy controls, but seroconversion rates in patients with more severe IEI, such as CVID and combined B- and T-cell immunodeficiency, were lower. Binding antibody titers correlated well to the presence of neutralizing antibodies. T-cell responses were comparable to those in controls in all IEI cohorts, with the exception of patients with CVID. The presence of noninfectious complications and the use of immunosuppressive drugs in patients with CVID were negatively correlated with the antibody response. CONCLUSIONS: COVID-19 vaccination with mRNA-1273 was immunogenic in mild antibody deficiencies and phagocyte defects and in most patients with combined B- and T-cell immunodeficiency and CVID. Lowest response was detected in patients with X-linked agammaglobulinemia and in patients with CVID with noninfectious complications. The assessment of longevity of immune responses in these vulnerable patient groups will guide decision making for additional vaccinations.

Frailty Is Associated With Mortality and Incident Comorbidity Among Middle-Aged Human Immunodeficiency Virus (HIV)-Positive and HIV-Negative Participants.

BACKGROUND: Frailty is associated with mortality and morbidity in the general geriatric population, but less is known about its impact among the aging but generally younger population with human immunodeficiency virus (HIV). METHODS: The impact of frailty on all-cause mortality during 6 years of follow-up and incident comorbidity during 4 years of follow-up was assessed among 598 HIV-positive and 550 comparable HIV-negative participants aged ≥ 45 years of the AGEhIV Cohort Study. Frailty encompasses 5 domains; weight loss, low physical activity, exhaustion, decreased grip strength, and slow gait speed. Presence of ≥ 3 denotes frailty, 1-2 prefrailty, and 0 robust. Multivariable Cox and logistic regression models were used to assess the independent relationships of frailty with both outcomes, adjusting for HIV infection and traditional risk factors. RESULTS: At baseline, 7.5% (n = 86) of participants were frail. During follow-up, 38 participants died. Mortality rate was significantly higher among frail participants: 25.7/1000 person-years of follow-up (PYFU) (95% confidence interval [CI], 14.2-46.4) compared with prefrail (7.2/1000 PYFU [95% CI, 4.7-11.2]) and robust (2.3/1000 PYFU [95% CI, 1.1-4.9]). In fully adjusted analyses, frailty remained strongly associated with death (hazard ratio, 4.6 [95% CI, 1.7-12.5]) and incident comorbidity (odds ratio, 1.9 [95% CI, 1.1-3.1]). No interactions were observed between frailty and HIV status in all analyses. CONCLUSIONS: Frailty is a strong predictor of both mortality and incident comorbidity independent from other risk factors. CLINICAL TRIALS REGISTRATION: NCT01466582.

[New antibiotics: an overview]. / Nieuwe antibiotica: een overzicht.

The worldwide rapid increase in antibiotic resistance means that new therapeutic measures are urgently needed. Older antibiotics, such as colistin, fosfomycin, minocycline, mecillinam and temocillin, which had fallen from grace due to the development of more effective and less toxic drugs are now of renewed interest in the treatment of infections caused by multiresistant bacteria. Two new glycopeptides (oritavancin and dalbavancin) and a new oxazolidinone (tedizolid) are now registered for the treatment of acute skin and soft-tissue infections. In the treatment of infections caused by Gram-negative bacteria, cephalosporins are combined with beta-lactamase inhibitors which protect them from various beta-lactamases and also make them effective against extended spectrum beta-lactamase-producing bacteria. Examples of these are ceftolozane-tazobactam, ceftazidime-avibactam and meropenem-vaborbactam. Results of preclinical research on the effectiveness of new antibiotics are hopeful. There has been a great increase in investment in the development of new antimicrobials. Also, regulatory agencies have accelerated their assessment of these new - and urgently needed - drugs.

Damage of the endothelial glycocalyx in dialysis patients.

Damage to the endothelial glycocalyx, which helps maintain vascular homeostasis, heightens the sensitivity of the vasculature to atherogenic stimuli. Patients with renal failure have endothelial dysfunction and increased risk for cardiovascular morbidity and mortality, but the state of the endothelial glycocalyx in these patients is unknown. Here, we used Sidestream Darkfield imaging to detect changes in glycocalyx dimension in dialysis patients and healthy controls from in vivo recordings of the sublingual microcirculation. Dialysis patients had increased perfused boundary region and perfused diameters, consistent with deeper penetration of erythrocytes into glycocalyx, indicating a loss of glycocalyx barrier properties. These patients also had higher serum levels of the glycocalyx constituents hyaluronan and syndecan-1 and increased hyaluronidase activity, suggesting the shedding of these components. Loss of residual renal function had no influence on the imaging parameters but did associate with greater shedding of hyaluronan in blood. Furthermore, patients with higher levels of inflammation had more significant damage to the glycocalyx barrier. In conclusion, these data suggest that dialysis patients have an impaired glycocalyx barrier and shed its constituents into blood, likely contributing to the sustained endothelial cell activation observed in ESRD.

The glycocalyx and cardiovascular disease in diabetes: should we judge the endothelium by its cover?

Patients with diabetes mellitus are characterized by an extraordinary vascular vulnerability. Traditionally, glucose-induced damage to the vascular endothelium is believed to be one of the first steps in the development of vascular damage. However, in the healthy vessel the endothelium is protected by a matrix layer of highly glycosylated proteins that form a physical barrier between the endothelium and the blood flowing past. Although its presence has been known for half a century, this so-called glycocalyx earned little attention from researchers in the past because of an underestimation of its size. In the last decade it has become clear that its full thickness actually exceeds that of the vascular endothelium. Accumulating research into the functional relevance of the endothelial glycocalyx suggests an important role for this layer in the development of cardiovascular disease in diabetes mellitus. Here we will present an overview of the biochemistry of the intact glycocalyx, current methods to assess the glycocalyx, and its possible role in the pathophysiology of cardiovascular disease in diabetes.