The Human Antibody Response to Staphylococcus Aureus in Colonization and Infection

__Abstract_ __Introduction__: Treatment options for Staphylococcus aureus infections are becoming increasingly limited because of the extensive emergence of antimicrobial resistance among S. aureus isolates. Consequently, novel approaches, including vaccines and immunotherapy, are urgently needed. In order to develop such alternative strategies, a better understanding of the human antibody response to S. aureus exposure, is necessary. __Methods__: The qualitative and quantitative levels of antibodies directed to important S. aureus cell wall-associated proteins, immune-modulating proteins and toxins were measured in healthy individuals, children and patients suffering from diverse S. aureus infections. A flow cytometry technique based on differentially coloured microspheres was used (xMAP® Technology). __Results__: In patients as well as in healthy children and adults, the antistaphylococcal antibody profiles showed extensive inter-individual variability. When groups were compared and significant differences were found, the level of antistaphylococcal antibodies was hi

Concomitant endocarditis and spondylodiscitis due to coagulase-negative Staphylococci and a review of the literature

Background: Coagulase-negative staphylococci (CoNS) are part of the normal skin flora. Although CoNS are generally considered as low pathogenic microorganisms, they can cause serious infections, particularly in the context of foreign body material. Case report: Here we present two cases of concomitant infectious endocarditis and spondylodiscitis; one caused by S. epidermidis, the other by S. haemolyticus. Additionally, we reviewed the literature for previously reported cases of concomitant endocarditis and spondylodiscitis due to CoNS. Conclusion: In patients with back pain and a cardiac device in situ, CoNS should be considered as causative pathogens for possible endocarditis and/or spondylodiscitis, and should not be regarded as contamination.</p

Best practices, implementation and challenges of outpatient parenteral antimicrobial therapy:results of a worldwide survey among healthcare providers.

Background: Outpatient Parenteral Antimicrobial Therapy (OPAT) is considered a patient-friendly and cost-effective practice. Patients in the OPAT service can be at risk for developing adverse events. Due to extensive variations in practice, guidelines have been developed to minimize the risks. Objectives: In this first worldwide survey on OPAT, we explored the current OPAT services around the world, adherence to recommendations and identified best practices and challenges from different perspectives. Methods: An e-survey was conducted and consisted of questions about demographics, characteristics of the OPAT service, role of pharmacy, future developments, and respondents’ views on improvements as well as best practices. Results: A total of 126 responses from 28 countries were included. Seventy-eight percent (78%) of the respondents stated that their facility provides antimicrobial therapy in the outpatient setting, whereas 22% did not. Forty-two percent (42%) of the hospitals with OPAT services had a specialized OPAT service, while 14% lacked specialized services and 22% had a partially specialized team in place. In facilities with a specialized OPAT service, the number of mandatory infectious disease (ID) consultations before discharge and clinical monitoring by an ID specialist or OPAT team member, the frequency of monitoring, and the availability of an OPAT registry were higher. A multidisciplinary team’s presence was commonly noted as best practices. On the other hand, respondents experienced difficulties with reimbursement and lack of standardization in the screening, follow-up and monitoring of patients. Conclusion: This survey provides a better understanding of the implementation and practices of OPAT services globally and describes best practices and the challenges from different professionals.</p

Contact tracing for vancomycin-resistant Enterococcus faecium (VRE):evaluation of the Dutch policy of quintuple screening cultures

Detection of vancomycin-resistant Enterococcus faecium (VRE) is hampered by low sensitivity of rectal swab cultures. This study aimed to define the number of screening cultures needed to increase sensitivity to detect VRE transmission, and to determine time from presumed exposure to detectable colonization. In a tertiary care setting, we retrospectively analyzed data from 9 VRE outbreaks. As a proxy or estimation for time to detectable colonization, the time between first positive culture of the presumed index patient and that of their contacts was determined. Only 64% of secondary cases were positive in the first out of five cultures. By using the first three out of five rectal swabs, 89% (95%CI: 78–95%) of all secondary cases would have been identified. The median number of days between the positive culture of the index patient and the first positive culture of secondary cases was 9 days. Eleven percent of secondary cases would have been missed if only three rectal samples would have been obtained. Furthermore, our results show that one or more rectal swabs taken around day 9 after presumed exposure should at least be included in the screening approach. In our setting, obtaining a fourth and a fifth rectal swab showed a relevant additional value compared to only one to three swabs. Our findings are useful for determining the most effective VRE contact tracing approach to prevent transmission.</p

The endocarditis team

Endocarditis is een ernstig ziektebeeld met een hoge mortaliteit en morbiditeit. In de klinische praktijk proberen we de behandeling van deze patiënten te verbeteren door goede en snelle diagnostiek en door tijdig adequate antibiotische en zo nodig chirurgische therapie te starten. In de nieuwste richtlijnen wordt het begrip ‘endocarditisteam’ geïntroduceerd als cruciaal onderdeel in de verbetering van de zorg voor patiënten met (een verdenking op) endocarditis. Er wordt gesteld dat endocarditis een multidisciplinaire aanpak vraagt omdat het een ziekte is met een grote variatie in presentatie, waarvoor expertise nodig is van verschillende specialisaties, en ook omdat patiënten in een vroege fase dienen te worden besproken in een chirurgisch team. Observationele studies tonen een belangrijke reductie in de mortaliteit van endocarditispatiënten die zijn besproken in een endocarditisteam.Dit artikel bespreekt de ervaringen met het opzetten van een endocarditisteam in twee verschillende regio’s in Nederland (Rotterdam-​Rijnmond en Groningen). Wat is belangrijk als het gaat om de structuur en functie van een endocarditisteam? Het opzetten van een endocarditisteam kan lastig zijn. Daarom geven we enkele praktische tips. Ten slotte wordt de toegevoegde waarde van een operationeel endocarditisteam geïllustreerd aan de hand van een casus.Endocarditis is a life-​threatening disease with high mortality and morbidity. In clinical practice, we try to improve the outcome of patients with endocarditis by implementing a better and faster diagnostic workup, a timely start of antimicrobial therapy and an early surgical intervention if required. In the most recent update of the guidelines for the management of patients with endocarditis, an Endocarditis team is put forward as crucial part in the improvement of care for patients with (suspected) endocarditis. They state that endocarditis requires a multidisciplinary approach since patients present with highly variable signs and symptoms, need a high-​standard of care from several medical specialists, and need to be discussed in a surgical team early in the course of the disease. Observational studies support this implementation by showing a marked decrease in mortality after dicussing endocarditis patients in an Endocarditis team. This article discusses the experience with the implementation of an Endocarditis team in two different regions of the Netherlands (Rotterdam-​Rijnmond and Groningen). Which aspects are important for the structure and function of an Endocarditis team? The setting up of an Endocarditis team can be difficult, therefore we provide some practical advice. Finally, an illustrative case is presented

Mycobacterium chelonae, an ‘atypical’ cause of an LVAD driveline infection

We describe the first patient with a left ventricular assist device (LVAD) driveline infection caused by Mycobacterium chelonae presenting with persistent infection despite conventional antibiotics. Treatment was successful with surgical debridement, driveline exit relocation, and a 4-month period of antibiotics. In the case of a culture-negative LVAD driveline infection, non-tuberculous mycobacteria should be considered. This case illustrates tha

Left ventricular assist device-related infections and the risk of cerebrovascular accidents:a EUROMACS study

OBJECTIVES: In patients supported by a durable left ventricular assist device (LVAD), infections are a frequently reported adverse event with increased morbidity and mortality. The purpose of this study was to investigate the possible association between infections and thromboembolic events, most notable cerebrovascular accidents (CVAs), in LVAD patients. METHODS: An analysis of the multicentre European Registry for Patients Assisted with Mechanical Circulatory Support was performed. Infections were categorized as VAD-specific infections, VAD-related infections and non-VAD-related infections. An extended Kaplan–Meier analysis for the risk of CVA with infection as a time-dependent covariate and a multivariable Cox proportional hazard model were performed. RESULTS: For this analysis, 3282 patients with an LVAD were included with the majority of patients being male (83.1%). During follow-up, 1262 patients suffered from infection, and 457 patients had a CVA. Cox regression analysis with first infection as time-dependent covariate revealed a hazard ratio (HR) for CVA of 1.90 [95% confidence interval (CI): 1.55–2.33; P < 0.001]. Multivariable analysis confirmed the association for infection and CVAs with an HR of 1.99 (95% CI: 1.62–2.45; P < 0.001). With infections subcategorized, VAD-specific HR was 1.56 (95% CI: 1.18–2.08; P 0.002) and VAD-related infections [HR: 1.99 (95% CI: 1.41–2.82; P < 0.001)] remained associated with CVAs, while non-VAD-related infections (P = 0.102) were not. CONCLUSIONS: Infection during LVAD support is associated with an increased risk of developing an ischaemic or haemorrhagic CVA, particularly in the setting of VAD-related or VAD-specific infections. This suggests the need of a stringent anticoagulation management and adequate antibiotic treatment during an infection in LVAD-supported patients

Characterization of the Humoral Immune Response during Staphylococcus aureus Bacteremia and Global Gene Expression by Staphylococcus aureus in Human Blood

Attempts to develop an efficient anti-staphylococcal vaccine in humans have so far been unsuccessful. Therefore, more knowledge of the antigens that are expressed by Staphylococcus aureus in human blood and induce an immune response in patients is required. In this study we further characterize the serial levels of IgG and IgA antibodies against 56 staphylococcal antigens in multiple serum samples of 21 patients with a S. aureus bacteremia, compare peak IgG levels between patients and 30 non-infected controls, and analyze the expression of 3626 genes by two genetically distinct isolates in human blood. The serum antibody levels were measured using a bead-based flow cytometry technique (xMAP®, Luminex corporation). Gene expression levels were analyzed using a microarray (BμG@s microarray). The initial levels and time taken to reach peak IgG and IgA antibody levels were heterogeneous in bacteremia patients. The antigen SA0688 was associated with the highest median initial-to-peak antibody fold-increase for IgG (5.05-fold) and the second highest increase for IgA (2.07-fold). Peak IgG levels against 27 antigens, including the antigen SA0688, were significantly elevated in bacteremia patients versus controls (P≤0.05). Expression of diverse genes, including SA0688, was ubiquitously high in both isolates at all time points during incubation in blood. However, only a limited number of genes were specifically up- or downregulated in both isolates when cultured in blood, compared to the start of incubation in blood or during incubation in BHI broth. In conclusion, most staphylococcal antigens tested in this study, including many known virulence factors, do not induce uniform increases in the antibody levels in bacteremia patients. In addition, the expression of these antigens by S. aureus is not significantly altered by incubation in human blood over time. One immunogenic and ubiquitously expressed antigen is the putative iron-regulated ABC transporter SA0688