46 results on '"Verkaik NJ"'
Search Results
2. Antimicrobial susceptibility to last-resort antibiotics in carbapenemase-producing bacteria from Ukrainian patients.
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Verkaik NJ, Wielders CCH, den Boer H, Langerak D, Vogel M, Witteveen S, de Haan A, Bos J, van Westreenen M, Notermans DW, and Hendrickx APA
- Abstract
Since March 2022, an increase was observed in multidrug-resistant microorganisms (MDRO), associated with the hospital transfer of Ukrainian patients. The goal was to collect phenotypic susceptibility data and assess clinical implications. Carbapenemase-producing Enterobacterales (CPE, n = 96), Pseudomonas aeruginosa (CPPA, n = 20), and carbapenem-resistant Acinetobacter baumannii-calcoaceticus (CRAB, n = 6) from Ukrainian patients were obtained from March to December 2022 from the Dutch MDRO surveillance. Antimicrobial susceptibility testing was performed using broth microdilution (BMD) when available, fosfomycin agar dilution, disk diffusion (DD) for cefiderocol, and diverse gradient strips. All isolates were sequenced with Illumina next-generation sequencing. For meropenem, aminoglycosides, ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-relebactam, susceptibility rates were low (0%-30%), due to the high number of bla
NDM -positive isolates (79/122; 65%). For cefiderocol, results depended on reading with or without microcolonies, applying EUCAST or CLSI breakpoints, and whether DD or BMD was used; e.g., for Klebsiella pneumoniae , 30%-97% were susceptible. For colistin, 103/111 (93%) non-intrinsically resistant CPE/CPPA/CRAB isolates were susceptible. For most CPE, a low minimal inhibitory concentration (MIC) of <0.5 mg/L was measured for tigecycline and ceftazidime-avibactam-aztreonam. For CPPA, cefiderocol tested susceptible in 65%-100% of isolates. For CRAB, ampicillin-sulbactam MICs were ≥128 mg/L; for sulbactam-durlobactam, 1-2 mg/L. Admission in a Ukrainian hospital in the last year was a risk factor for MDRO, and majority were screening isolates (79%). There is extensive phenotypic resistance to last-resort antibiotics in MDRO from Ukrainian patients. Interpretation of cefiderocol susceptibility results depends on several variables. When treating patients recently admitted in Ukraine, suspected for Gram-negative bacterial infection, this should be taken into consideration., Importance: Since March 2022, multidrug-resistant microorganisms associated with Ukrainian patients have been detected in national surveillance systems of several European countries. We studied the phenotypic antimicrobial susceptibility to last-resort antibiotics of multidrug-resistant microorganisms from Ukrainian patients in the Netherlands and assessed clinical implications. Our research revealed that there was extensive phenotypic resistance to last-resort antibiotics. Healthcare professionals should be aware of multidrug-resistant microorganisms when treating patients recently admitted in Ukraine, suspected for Gram-negative bacterial infection.- Published
- 2024
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3. Target attainment of beta-lactam antibiotics and ciprofloxacin in critically ill patients and its association with 28-day mortality.
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Dräger S, Ewoldt TMJ, Abdulla A, Rietdijk WJR, Verkaik NJ, van Vliet P, Purmer IM, Osthoff M, Koch BCP, and Endeman H
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Objectives: This study aims to assess pharmacodynamic target attainment in critically ill patients and identify factors influencing target attainment and mortality outcomes., Methods: We analysed data from the DOLPHIN trial. Beta-lactam and ciprofloxacin peak and trough concentration were measured within the first 36 h (T1) after initiation of treatment. The study outcome included the rate of pharmacodynamic target attainment of 100 % ƒT
>1xEpidemiological cut-off value (ECOFF) for beta-lactams, and of fAUC0-24h /ECOFF>125 for ciprofloxacin at T1., Results: The target attainment rates were 78.1 % (n = 228/292) for beta-lactams, and 41.5 % (n = 39/94) for ciprofloxacin, respectively. Lower estimated glomerular filtration rate and higher SOFA score were associated with target attainment. In patients receiving beta-lactams, 28-day mortality was significantly higher in patients who attained 100 % ƒT>1xECOFF (28.9 % vs. 12.5 %; p = 0.01). In the multivariate analysis, attainment of 100 % ƒT>4xECOFF , but not 100 % ƒT>1xECOFF , was associated with a higher 28-day mortality (OR 2.70, 95 % CI 1.36-5.48 vs. OR 1.28, 95 % CI 0.53-3.34)., Conclusions: A high rate of target attainment (100 % ƒT>1xECOFF ) for beta-lactams and a lower rate for ciprofloxacin was observed. Achieving exposures of 100 % ƒT>4xECOFF was associated with 28-day mortality. The impact of antibiotic target attainment on clinical outcome needs to be a focus of future research., Competing Interests: Declaration of competing interest BCPK reports grants or contracts unrelated to this work from IMI, European Union, and Prinses Beatrix Foundation; Foundation Coolsingel; a role as unpaid Board member for IATDMCT, ESCMID EPASG, SWAB. All other authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)- Published
- 2024
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4. Best practices, implementation and challenges of outpatient parenteral antimicrobial therapy: results of a worldwide survey among healthcare providers.
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Hassanzai M, Adanç F, Koch BCP, Verkaik NJ, van Oldenrijk J, de Bruin JL, de Winter BCM, and van Onzenoort HAW
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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., Competing Interests: The authors declare that there is no conflict of interest., (© The Author(s), 2023.)
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- 2023
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5. Less Is More: When to Repeat Antimicrobial Susceptibility Testing.
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Sarink MJ, Bode LGM, Croughs P, de Steenwinkel JEM, Verkaik NJ, van Westreenen M, Vogel M, and Yusuf E
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- Humans, Drug Resistance, Bacterial, Anti-Bacterial Agents pharmacology, Bacteria, Pseudomonas aeruginosa, Microbial Sensitivity Tests, Escherichia coli, Staphylococcus aureus
- Abstract
This study investigated the frequency of change of the antimicrobial susceptibility pattern when the same isolate was found in the same patient in various situations. We used laboratory data collected over a period of 8 years (January 2014 to December 2021) at the clinical microbiology laboratory of a tertiary hospital for Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Pseudomonas aeruginosa, and Staphylococcus aureus. Antimicrobial susceptibility tests (AST) were performed using Vitek 2 automated system. We determined essential agreement and categorical agreement, and introduced the new terms essential MIC increase and change from nonresistant to resistant to present changes in antimicrobial susceptibility over time. During the study period, 18,501 successive AST were included. The risk for S. aureus to be resistant to any antibiotic upon repeated culture was <10% during a follow-up of 30 days. For Enterobacterales, this risk was approximately 10% during a follow-up of 7 days. For P. aeruginosa, this risk was higher. The longer the follow-up period, the higher the risk that the bacteria would show phenotypic resistance. We also found that some drug-bug combinations were more likely to develop phenotypical resistance (i.e., E. coli/amoxicillin-clavulanic acid and E. coli/cefuroxime). A potential consequence of our finding is that if we regard a risk of resistance below 10% as acceptable, it may be feasible to omit follow-up AST within 7 days for the microorganisms investigated in this study. This approach saves money, time, and will reduce laboratory waste. Further studies are needed to determine whether these savings are in balance with the small possibility of treating patients with inadequate antibiotics., Competing Interests: The authors declare no conflict of interest.
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- 2023
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6. Contact tracing for vancomycin-resistant Enterococcus faecium (VRE): evaluation of the Dutch policy of quintuple screening cultures.
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Wammes LJ, Voor In 't Holt AF, Klaassen CHW, Vos MC, Verkaik NJ, and Severin JA
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- Humans, Vancomycin, Contact Tracing, Retrospective Studies, Anti-Bacterial Agents therapeutic use, Enterococcus faecium, Vancomycin-Resistant Enterococci, Gram-Positive Bacterial Infections diagnosis, Gram-Positive Bacterial Infections epidemiology, Gram-Positive Bacterial Infections microbiology
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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., (© 2023. The Author(s).)
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- 2023
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7. Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment.
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Buis D, van Werkhoven CH, van Agtmael MA, Bax HI, Berrevoets M, de Boer M, Bonten M, Bosmans JE, Branger J, Douiyeb S, Gelinck L, Jong E, Lammers A, Van der Meer J, Oosterheert JJ, Sieswerda E, Soetekouw R, Stalenhoef JE, Van der Vaart TW, Bij de Vaate EA, Verkaik NJ, Van Vonderen M, De Vries PJ, Prins JM, and Sigaloff K
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- Adult, Humans, Anti-Bacterial Agents, Duration of Therapy, Staphylococcus aureus, Randomized Controlled Trials as Topic, Multicenter Studies as Topic, Staphylococcal Infections drug therapy, Staphylococcal Infections microbiology, Bacteremia microbiology
- Abstract
Introduction: A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB., Methods and Analysis: The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study., Ethics and Dissemination: This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal., Trial Registration Number: NL8347 (the Netherlands Trial Register)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
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8. The impact of the multidisciplinary Endocarditis Team on the management of infective endocarditis.
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Wahadat AR, Tanis W, Galema TW, Swart LE, van Leeuwen WJ, Verkaik NJ, Schurink CAM, van Dalen B, Zoet-Nugteren S, Gurlek C, Budde RPJ, and Roos-Hesselink JW
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Background: In their latest guidelines for infective endocarditis (IE) (2015), the European Society of Cardiology (ESC) introduced the implementation of the Endocarditis Team (ET) to facilitate the management of IE. This study presents our experiences and the diagnostic and therapeutic impact of the ET on the management of IE., Methods: From 2016-2020, data of all patients with suspected IE referred to the ET were prospectively collected. The final diagnosis was defined by the ET as either rejected, possible or definite IE. Diagnostic impact was scored as any change in initial diagnosis, the frequency of additional diagnostic tests advised by the ET and any change in diagnosis after these tests. Therapeutic impact was scored as any change in antibiotic therapy or change from conservative to invasive therapy or vice versa., Results: A total of 321 patients (median age 67 [55-77] years, 71% male) were enrolled. The final diagnosis was rejected IE in 47 (15%), possible IE in 34 (11%) and definite IE in 240 (75%) patients. A change of initial diagnosis was seen in 53/321(17%) patients. Additional microbiological tests were advised in 69/321 (21%) patients, and additional imaging tests in 136/321 (42%) patients, which resulted in subsequent change in diagnosis in 23/321 (7%) patients. Any change in antibiotic treatment was advised in 135/321 (42%) patients, and change from initial conservative to additional surgical treatment in 15/321 (5%) patients., Conclusion: The ET had a clear impact on the therapeutic policy for patients with suspected IE and is useful in the management of this life-threatening disease. Broad implementation is warranted., (© 2022. The Author(s).)
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- 2023
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9. Pseudomonas aeruginosa left ventricular assist device (LVAD) driveline infection acquired from the bathroom at home.
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Dix LML, de Goeij I, Manintveld OC, Severin JA, and Verkaik NJ
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- Humans, Pseudomonas aeruginosa, Toilet Facilities, Heart-Assist Devices adverse effects, Pseudomonas Infections, Prosthesis-Related Infections
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We describe a patient with a left ventricular assist device (LVAD) infection by Pseudomonas aeruginosa acquired at home. The Pseudomonas from the driveline was similar to several surface cultures of the patient's home shower. This case illustrates the potential and importance of infection prevention measures at home., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2022
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10. Multidrug-resistant organisms in patients from Ukraine in the Netherlands, March to August 2022.
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Zwittink RD, Wielders CC, Notermans DW, Verkaik NJ, Schoffelen AF, Witteveen S, Ganesh VA, de Haan A, Bos J, Bakker J, Schneeberger-van der Linden C, Kuijper EJ, de Greeff SC, and Hendrickx AP
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- Humans, Netherlands epidemiology, Ukraine epidemiology, Gram-Negative Bacteria, beta-Lactamases genetics, Microbial Sensitivity Tests, Anti-Bacterial Agents pharmacology, Drug Resistance, Multiple, Bacterial genetics
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Since March 2022, there has been an emergence of multidrug-resistant organisms (MDRO) in the Netherlands in patients originating from Ukraine (58 patients, 75 isolates). For about half of these patients, recent hospitalisation in Ukraine was reported. Genomic surveillance revealed that the majority of the MDRO represent globally spread epidemic lineages and that 60% contain New Delhi metallo-β-lactamase (NDM) genes. Professionals should be aware of an increase in such MDRO associated with migration and medical evacuation of people from Ukraine.
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- 2022
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11. Left ventricular assist device-related infections and the risk of cerebrovascular accidents: a EUROMACS study.
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Zijderhand CF, Antonides CFJ, Veen KM, Verkaik NJ, Schoenrath F, Gummert J, Nemec P, Merkely B, Musumeci F, Meyns B, de By TMMH, Bogers AJJC, and Caliskan K
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- Anti-Bacterial Agents, Anticoagulants, Female, Humans, Male, Registries, Retrospective Studies, Treatment Outcome, Heart Failure, Heart-Assist Devices adverse effects, Stroke epidemiology, Stroke etiology
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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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)
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- 2022
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12. Native valve, prosthetic valve, and cardiac device-related infective endocarditis: A review and update on current innovative diagnostic and therapeutic strategies.
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Kouijzer JJP, Noordermeer DJ, van Leeuwen WJ, Verkaik NJ, and Lattwein KR
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Infective endocarditis (IE) is a life-threatening microbial infection of native and prosthetic heart valves, endocardial surface, and/or indwelling cardiac device. Prevalence of IE is increasing and mortality has not significantly improved despite technological advances. This review provides an updated overview using recent literature on the clinical presentation, diagnosis, imaging, causative pathogens, treatment, and outcomes in native valve, prosthetic valve, and cardiac device-related IE. In addition, the experimental approaches used in IE research to improve the understanding of disease mechanisms and the current diagnostic pipelines are discussed, as well as potential innovative diagnostic and therapeutic strategies. This will ultimately help towards deriving better diagnostic tools and treatments to improve IE patient outcomes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kouijzer, Noordermeer, van Leeuwen, Verkaik and Lattwein.)
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- 2022
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13. Single-Center Experience With Protocolized Treatment of Left Ventricular Assist Device Infections.
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Verkaik NJ, Yalcin YC, Bax HI, Constantinescu AA, Brugts JJ, Manintveld OC, Birim O, Croughs PD, Bogers AJJC, and Caliskan K
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Purpose: Because of the current lack of evidence-based antimicrobial treatment guidelines, Left Ventricular Assist Device (LVAD) infections are often treated according to local insights. Here, we propose a flowchart for protocolized treatment, in order to improve outcome., Methods: The flowchart was composed based on literature, consensus and expert opinion statements. It includes choice, dosage and duration of antibiotics, and indications for suppressive therapy, with particular focus on Staphylococcus aureus (SA) (Figure 1). The preliminary treatment results of 28 patients (2 from start cephalexin suppressive therapy) after implementation in July 2018 are described., Results: Cumulative incidence for first episode of infection in a 3-year time period was 27% (26 of 96 patients with an LVAD). Twenty-one of 23 (91%) first episodes of driveline infection (10 superficial and 13 deep; nine of 13 caused by SA) were successfully treated with antibiotics according to flowchart with complete resolution of clinical signs and symptoms. For two patients with deep driveline infections, surgery was needed in addition. There were no relapses of deep driveline infections, and only 2 SA deep driveline re-infections after 6 months. Nine patients received cephalexin of whom four patients (44%) developed a breakthrough infection with cephalexin-resistant gram-negative bacteria., Conclusions: The first results of this protocolized treatment approach of LVAD infections are promising. Yet, initiation of cephalexin suppressive therapy should be carefully considered given the occurrence of infections with resistant micro-organisms. The long-term outcome of this approach needs to be established in a larger number of patients, preferably in a multi-center setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Verkaik, Yalcin, Bax, Constantinescu, Brugts, Manintveld, Birim, Croughs, Bogers and Caliskan.)
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- 2022
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14. Real time monitoring of Staphylococcus aureus biofilm sensitivity towards antibiotics with isothermal microcalorimetry.
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Sultan AR, Tavakol M, Lemmens-den Toom NA, Croughs PD, Verkaik NJ, Verbon A, and van Wamel WJB
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- Floxacillin pharmacology, Genetic Linkage, Methicillin-Resistant Staphylococcus aureus genetics, Methicillin-Resistant Staphylococcus aureus physiology, Microbial Sensitivity Tests, Rifampin pharmacology, Staphylococcus aureus genetics, Vancomycin pharmacology, Anti-Bacterial Agents pharmacology, Biofilms drug effects, Calorimetry methods, Staphylococcus aureus physiology
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Biofilm-associated infections with Staphylococcus aureus are difficult to treat even after administration of antibiotics that according to the standard susceptibility assays are effective. Currently, the assays used in the clinical laboratories to determine the sensitivity of S. aureus towards antibiotics are not representing the behaviour of biofilm-associated S. aureus, since these assays are performed on planktonic bacteria. In research settings, microcalorimetry has been used for antibiotic susceptibility studies. Therefore, in this study we investigated if we can use isothermal microcalorimetry to monitor the response of biofilm towards antibiotic treatment in real-time. We developed a reproducible method to generate biofilm in an isothermal microcalorimeter setup. Using this system, the sensitivity of 5 methicillin-sensitive S. aureus (MSSA) and 5 methicillin-resistant S. aureus (MRSA) strains from different genetic lineages were determined towards: flucloxacillin, cefuroxime, cefotaxime, gentamicin, rifampicin, vancomycin, levofloxacin, clindamycin, erythromycin, linezolid, fusidic acid, co-trimoxazole, and doxycycline. In contrast to conventional assays, our calorimetry-based biofilm susceptibility assay showed that S. aureus biofilms, regardless MSSA or MRSA, can survive the exposure to the maximum serum concentration of all tested antibiotics. The only treatment with a single antibiotic showing a significant reduction in biofilm survival was rifampicin, yet in 20% of the strains, emerging antibiotic resistance was observed. Furthermore, the combination of rifampicin with flucloxacillin, vancomycin or levofloxacin was able to prevent S. aureus biofilm from becoming resistant to rifampicin. Isothermal microcalorimetry allows real-time monitoring of the sensitivity of S. aureus biofilms towards antibiotics in a fast and reliable way., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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15. Driveline exit-site care protocols in patients with left ventricular assist devices: a systematic review.
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Koken ZO, Yalcin YC, van Netten D, de Bakker CC, van der Graaf M, Kervan U, Verkaik NJ, and Caliskan K
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- Clinical Protocols, Heart Ventricles, Humans, Prospective Studies, Heart Failure therapy, Heart-Assist Devices adverse effects, Prosthesis-Related Infections epidemiology, Prosthesis-Related Infections prevention & control
- Abstract
Objectives: Driveline infections continue to be a significant complication following left ventricular assist device (LVAD) implantation. Driveline exit-site care is crucial for the prevention of infections; however, there are no uniform guidelines. The goal of this study was to provide an overview of the currently published driveline exit-site care protocols in patients with LVAD., Methods: A systematic literature review was performed. Studies before 15 December 2020 were included if the number of driveline infections was a primary outcome and the driveline exit-site care protocol was explained., Results: Eleven articles were included in the systematic review, including 1602 patients with LVADs. The median of the frequency of driveline infections in the articles was 13.8% with a range of 0-52.6%. There was a marked variability in the methods of care of driveline exit sites, without a standardized driveline dressing technique in patients with LVADs. The frequency of driveline infections was 6-7.5% in studies using a dressing kit that included chlorhexidine, a silver-based dressing and an anchoring device. Furthermore, there was variability in the anchoring devices and the frequency of dressing changes, which varied from daily to weekly. No specific anchoring device or change frequency was found to be superior., Conclusions: Based on this systematic review, driveline exit care protocols that included chlorhexidine, a silver-based dressing, the use of an anchoring device and dressing kits might be best in reducing driveline infection rates. However, prospective studies with larger cohorts are needed to establish the optimal protocol for driveline exit-site care., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)
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- 2021
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16. New-Generation Antibiotics for Treatment of Gram-Positive Infections: A Review with Focus on Endocarditis and Osteomyelitis.
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Bloem A, Bax HI, Yusuf E, and Verkaik NJ
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Infective endocarditis, osteomyelitis, and osteosynthesis-associated infections are mostly caused by Gram-positive bacteria. They are often difficult to treat and are associated with a poor prognosis. In the past 20 years, nine antibiotic drugs with predominant activity against Gram-positive bacteria have been introduced and approved by the Food and Drug Administration or the European Medicines Agency: ceftaroline, daptomycin, telavancin, dalbavancin, oritavancin, linezolid, tedizolid, delafloxacin, and omadacycline. This narrative review aims to provide an overview on these antibiotics with a special focus on their use in infective endocarditis, osteomyelitis, and osteosynthesis-associated infections. Although some of these approved antibiotics are promising, they should not be used as first- or second-line therapy, awaiting more clinical data.
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- 2021
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17. Concomitant endocarditis and spondylodiscitis due to coagulase-negative Staphylococci and a review of the literature.
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Houkes KMG, Mudde SE, Constantinescu AA, Verkaik NJ, and Yusuf E
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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., Competing Interests: The authors report no declarations of interest., (© 2021 The Author(s).)
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- 2021
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18. An Update on Eight "New" Antibiotics against Multidrug-Resistant Gram-Negative Bacteria.
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Yusuf E, Bax HI, Verkaik NJ, and van Westreenen M
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Infections in the ICU are often caused by Gram-negative bacteria. When these microorganisms are resistant to third-generation cephalosporines (due to extended-spectrum (ESBL) or AmpC beta-lactamases) or to carbapenems (for example carbapenem producing Enterobacteriales (CPE)), the treatment options become limited. In the last six years, fortunately, there have been new antibiotics approved by the U.S. Food and Drug Administration (FDA) with predominant activities against Gram-negative bacteria. We aimed to review these antibiotics: plazomicin, eravacycline, temocillin, cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem/vaborbactam, and imipenem/relebactam. Temocillin is an antibiotic that was only approved in Belgium and the UK several decades ago. We reviewed the in vitro activities of these new antibiotics, especially against ESBL and CPE microorganisms, potential side effects, and clinical studies in complicated urinary tract infections (cUTI), intra-abdominal infections (cIAI), and hospital-acquired pneumonia/ventilator-associatedpneumonia (HAP/VAP). All of these new antibiotics are active against ESBL, and almost all of them are active against CPE caused by KPC beta-lactamase, but only some of them are active against CPE due to MBL or OXA beta-lactamases. At present, all of these new antibiotics are approved by the U.S. Food and Drug Administration for cUTI (except eravacycline) and most of them for cIAI (eravacycline, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam) and for HAP or VAP (cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and imipenem/relebactam).
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- 2021
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19. Frequency of Positive Aspergillus Tests in COVID-19 Patients in Comparison to Other Patients with Pulmonary Infections Admitted to the Intensive Care Unit.
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Yusuf E, Vonk A, van den Akker JPC, Bode L, Sips GJ, Rijnders BJA, de Steenwinkel J, Verkaik NJ, Vogel M, van der Eerden M, and van Westreenen M
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- Aged, Aspergillus, Bronchoalveolar Lavage Fluid, Female, Humans, Male, Mannans, Middle Aged, COVID-19 complications, Intensive Care Units, Invasive Pulmonary Aspergillosis diagnosis, Invasive Pulmonary Aspergillosis epidemiology
- Abstract
The aim of this study was to describe the frequency of positive Aspergillus tests in COVID-19 patients and investigate the association between COVID-19 and a positive Aspergillus test result. We compared the proportion of positive Aspergillus tests in COVID-19 patients admitted to the intensive care unit (ICU) for >24 h with two control groups: patients with community-acquired pneumonia with (i) a PCR-confirmed influenza infection (considered a positive control since the link between influenza and invasive aspergillosis has been established) and (ii) Streptococcus pneumoniae pneumonia (in whom positive Aspergillus tests are mostly considered as colonization). During the study period, 92 COVID-19 patients (mean [standard deviation] age, 62 [14] years; 76.1% males), 48 influenza patients (55 [14]; 56.2% males), and 65 pneumococcal pneumonia patients (58 [15], 63,1% males) were identified. Any positive Aspergillus test from any respiratory sample was found in 10.9% of the COVID-19 patients, 6.2% of the patients with pneumococcal pneumonia, and 22.9% of those infected with influenza. A positive culture or PCR or galactomannan test on bronchoalveolar lavage (BAL) fluid only was found in 5.4% of COVID-19 patients, which was lower than in patients with influenza (18.8%) and comparable to that in the pneumococcal pneumonia group (4.6%). Using logistic regression analysis, the odds ratio (OR) (95% confidence interval) for a positive Aspergillus test on BAL fluid for COVID-19 patients was 1.2 (0.3 to 5.1; P = 0.8) compared to the pneumococcal pneumonia group, while it was 0.2 (0.1 to 0.8; P = 0.02) compared to the influenza group. This difference remained significant when corrected for age and sex. In conclusion, in COVID-19 patients, the prevalence of a positive Aspergillus test was comparable to that in patients admitted for pneumococcal pneumonia but substantially lower than what we observed in patients with influenza., (Copyright © 2021 American Society for Microbiology.)
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- 2021
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20. Implementation of the 2015 European Society of Cardiology guidelines for the management of infective endocarditis in the Netherlands.
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Wahadat AR, Deckers JW, Budde RPJ, van der Meer JTM, Natour EH, Ten Oever J, Kortlever-van der Spek ALJ, Stegeman BH, Verkaik NJ, Roos-Hesselink JW, and Tanis W
- Abstract
Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called 'endocarditis team' in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC.
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- 2020
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21. Re: 'Critical factors in the recovery of pathogenic microorganisms in blood' by Wilson et al.
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Verkaik NJ, Yusuf E, and Croughs PD
- Abstract
Competing Interests: Transparency declaration All authors report no conflict of interests. No external funding was received.
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- 2020
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22. Use of stewardship smartphone applications by physicians and prescribing of antimicrobials in hospitals: A systematic review.
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Helou RI, Foudraine DE, Catho G, Peyravi Latif A, Verkaik NJ, and Verbon A
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- Antimicrobial Stewardship standards, Guideline Adherence trends, Hospitals, Humans, Anti-Infective Agents therapeutic use, Antimicrobial Stewardship methods, Mobile Applications, Physicians psychology, Practice Patterns, Physicians' standards
- Abstract
Background: Antimicrobial stewardship (AMS) programs promote appropriate use of antimicrobials and reduce antimicrobial resistance. Technological developments have resulted in smartphone applications (apps) facilitating AMS. Yet, their impact is unclear., Objectives: Systematically review AMS apps and their impact on prescribing by physicians treating in-hospital patients., Data Sources: EMBASE, MEDLINE (Ovid), Cochrane Central, Web of Science and Google Scholar., Study Eligibility Criteria: Studies focusing on smartphone or tablet apps and antimicrobial therapy published from January 2008 until February 28th 2019 were included., Participants: Physicians treating in-hospital patients., Interventions: AMS apps., Methods: Systematic review., Results: Thirteen studies met the eligibility criteria. None was a randomized controlled trial. Methodological study quality was considered low to moderate in all but three qualitative studies. The primary outcomes were process indicators, adherence to guidelines and user experience. Guidelines were more frequently accessed by app (53.0% - 89.6%) than by desktop in three studies. Adherence to guidelines increased (6.5% - 74.0%) significantly for several indications after app implementation in four studies. Most users considered app use easy (77.4%->90.0%) and useful (71.0%->90%) in three studies and preferred it over guideline access by web viewer or booklet in two studies. However, some physicians regarded app use adjacent to colleagues or patients unprofessional in three qualitative studies. Susceptibility to several antimicrobials changed significantly post-intervention (from 5% decrease to 10% - 14% increase) in one study., Conclusions: Use of AMS apps seems to promote access to and knowledge of antimicrobial prescribing policy, and increase adherence to guidelines in hospitals. However, this has been assessed in a limited number of studies and for specific indications. Good quality studies are necessary to properly assess the impact of AMS apps on antimicrobial prescribing. To improve adherence to antimicrobial guidelines, use of AMS apps could be considered., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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23. Neonatal Staphylococcus aureus acquisition at a tertiary intensive care unit.
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Slingerland BCGC, Verkaik NJ, Klaassen CHW, Zandijk WHA, Reiss IKM, and Vos MC
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- Humans, Infant, Newborn, Intensive Care Units, Neonatal, Staphylococcus aureus genetics, Whole Genome Sequencing, Bacteremia, Methicillin-Resistant Staphylococcus aureus genetics, Staphylococcal Infections epidemiology
- Abstract
Background: In this study, we explored the role of colonization in health care workers (HCWs) in transmission of methicillin-susceptible Staphylococcus aureus (MSSA) to neonates at a level IV neonatal intensive care unit (NICU)., Methods: All available screening and clinical MSSA isolates, from the period March 2015 through April 2016, isolated from HCWs and neonates at the level IV NICU, were included. MSSA isolates were initially genotyped using spa typing, and for the most prevalent spa types, whole-genome sequencing (WGS) was performed., Results: From March 2015 through April 2016, 159 neonates and 115 HCWs were found positive for MSSA, and all isolates were typed by means of spa typing. Twenty-three spa types were found in both HCWs and neonates. Within the most prevalent spa types (t002, t015 and t2787), 4 WGS clusters of genetically indistinguishable MSSA isolates were found in which 4 HCWs and 35 neonates were involved. A total of 10 neonates included in the 4 WGS clusters suffered from bacteremia., Conclusions: We showed that HCWs carried the same MSSA isolates as those found in neonates, and that HCWs might serve as a reservoir for transmission of MSSA to neonates. Ten neonates suffered from a bacteremia caused by a MSSA previously detected in a HCW., (Copyright © 2019 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)
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- 2020
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24. Mycobacterium chelonae, an 'atypical' cause of an LVAD driveline infection.
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Roest S, Bax HI, Verkaik NJ, Brugts JJ, Constantinescu AA, de Bakker CC, Birim O, Caliskan K, and Manintveld OC
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- Anti-Bacterial Agents therapeutic use, Debridement, Humans, Male, Middle Aged, Mycobacterium Infections, Nontuberculous therapy, Heart-Assist Devices adverse effects, Mycobacterium Infections, Nontuberculous etiology, Mycobacterium chelonae
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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 that multidisciplinary collaboration is essential in providing optimal care for LVAD patients., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2020
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25. Whole-genome sequencing to explore nosocomial transmission and virulence in neonatal methicillin-susceptible Staphylococcus aureus bacteremia.
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Slingerland BCGC, Vos MC, Bras W, Kornelisse RF, De Coninck D, van Belkum A, Reiss IKM, Goessens WHF, Klaassen CHW, and Verkaik NJ
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- Bacteremia microbiology, Bacterial Toxins genetics, Bacterial Typing Techniques, Cross Infection microbiology, Enterotoxins genetics, Female, Genome, Bacterial, Humans, Infant, Newborn, Intensive Care Units, Neonatal, Male, Multilocus Sequence Typing, Netherlands epidemiology, Retrospective Studies, Staphylococcus aureus genetics, Staphylococcus aureus isolation & purification, Superantigens genetics, Virulence, Bacteremia transmission, Cross Infection transmission, Staphylococcal Infections transmission, Staphylococcus aureus pathogenicity, Whole Genome Sequencing methods
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Background: Neonatal Staphylococcus aureus (S. aureus) bacteremia is an important cause of morbidity and mortality. In this study, we examined whether methicillin-susceptible S. aureus (MSSA) transmission and genetic makeup contribute to the occurrence of neonatal S. aureus bacteremia., Methods: A retrospective, single-centre study was performed. All patients were included who suffered from S. aureus bacteremia in the neonatal intensive care unit (NICU), Erasmus MC-Sophia, Rotterdam, the Netherlands, between January 2011 and November 2017. Whole-genome sequencing (WGS) was used to characterize the S. aureus isolates, as was also done in comparison to reference genomes. Transmission was considered likely in case of genetically indistinguishable S. aureus isolates., Results: Excluding coagulase-negative staphylococci (CoNS), S. aureus was the most common cause of neonatal bacteremia. Twelve percent (n = 112) of all 926 positive blood cultures from neonates grew S. aureus. Based on core genome multilocus sequence typing (cgMLST), 12 clusters of genetically indistinguishable MSSA isolates were found, containing 33 isolates in total (2-4 isolates per cluster). In seven of these clusters, at least two of the identified MSSA isolates were collected within a time period of one month. Six virulence genes were present in 98-100% of all MSSA isolates. In comparison to S. aureus reference genomes, toxin genes encoding staphylococcal enterotoxin A (sea) and toxic shock syndrome toxin 1 (tsst-1) were present more often in the genomes of bacteremia isolates., Conclusion: Transmission of MSSA is a contributing factor to the occurrence of S. aureus bacteremia in neonates. Sea and tsst-1 might play a role in neonatal S. aureus bacteremia.
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- 2020
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26. Partial Oral Therapy for Osteomyelitis and Endocarditis.
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Verkaik NJ, van der Vaart TW, and van der Meer JTM
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- Administration, Intravenous, Anti-Bacterial Agents, Humans, Endocarditis, Osteomyelitis
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- 2019
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27. Genomic Evolution of Staphylococcus aureus During Artificial and Natural Colonization of the Human Nose.
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Goyal M, Javerliat F, Palmieri M, Mirande C, van Wamel W, Tavakol M, Verkaik NJ, and van Belkum A
- Abstract
Staphylococcus aureus can colonize the human vestibulum nasi for many years. It is unknown whether and, how S. aureus adapts to this ecological niche during colonization. We determined the short (1 and 3 months) and mid-term (36 months) genomic evolution of S. aureus in natural carriers and artificially colonized volunteers. Eighty-five S. aureus strains were collected from 6 natural carriers during 3 years and 6 artificially colonized volunteers during 1 month. Multi-locus sequence typing (MLST) and single nucleotide polymorphism (SNP) analysis based on whole-genome sequencing (WGS) were carried out. Mutation frequencies within resident bacterial populations over time were quantified using core genome SNP counts (comparing groups of genomes) and pairwise SNP divergence assessment (comparing two genomes from strains originating from one host and sharing identical MLST). SNP counts (within 1-3 months) in all naturally colonizing strains varied from 0 to 757 (median 4). These strains showed random and independent patterns of pairwise SNP divergence (0 to 44 SNPs, median 7). When the different core genome SNP counts over a period of 3 years were considered, the median SNP count was 4 (range 0-26). Host-specific pairwise SNP divergence for the same period ranged from 9 to 57 SNPs (median 20). During short term artificial colonization the mutation frequency was even lower (0-7 SNPs, median 2) and the pairwise SNP distances were 0 to 5 SNPs (median 2). Quantifying mutation frequencies is important for the longitudinal follow-up of epidemics of infections and outbreak management. Random pattern of pairwise SNP divergence between the strains isolated from single carriers suggested that the WGS of multiple colonies is necessary in this context. Over periods up to 3 years, maximum median core genome SNP counts and SNP divergence for the strains studied were 4 and 20 SNPs or lower. During artificial colonization, where median core genome SNP and pairwise SNP distance scores were 2, there is no early stage selection of different genotypes. Therefore, we suggest an epidemiological cut off value of 20 SNPs as a marker of S. aureus strain identity during studies on nasal colonization and also outbreaks of infection.
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- 2019
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28. Massive diarrhoea and sepsis due to an infection with Neisseria meningitidis serogroup W.
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Houweling BM, van Meurs SJ, Versluis J, Grewal S, Verkaik NJ, and van den Akker JPC
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- Diagnosis, Differential, Diarrhea diagnosis, Female, Humans, Meningococcal Infections diagnosis, Sepsis diagnosis, Young Adult, Diarrhea microbiology, Meningococcal Infections complications, Meningococcal Infections microbiology, Neisseria meningitidis, Serogroup W-135, Sepsis microbiology
- Abstract
Invasive meningococcal disease is associated with significant mortality. Classic presentation consists of high fever, headache and neck stiffness. Neisseria meningitidis serogroup W may present with atypical symptoms, which complicates recognition. Furthermore, it is associated with a high case fatality rate.
- Published
- 2019
29. Antibiotic treatment of Propionibacterium acnes endocarditis.
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Verkaik NJ, Schurink CAM, and Melles DC
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- Endocarditis, Endocarditis, Bacterial, Gram-Positive Bacterial Infections, Humans, Anti-Bacterial Agents, Propionibacterium acnes
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- 2018
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30. eReply. Towards better understanding and management of Propionibacterium acnes in cases of prosthetic valve endocarditis.
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van Valen R, Verkaik NJ, Mokhles MM, and Bogers AJ
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- Gram-Positive Bacterial Infections microbiology, Heart Valve Prosthesis microbiology, Humans, Prosthesis-Related Infections microbiology, Endocarditis, Bacterial microbiology, Propionibacterium acnes
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- 2016
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31. Prosthetic valve endocarditis due to Propionibacterium acnes.
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van Valen R, de Lind van Wijngaarden RA, Verkaik NJ, Mokhles MM, and Bogers AJ
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- Adult, Aged, Anti-Bacterial Agents therapeutic use, Communicable Diseases, Endocarditis, Bacterial diagnosis, Endocarditis, Bacterial therapy, Female, Heart Valve Prosthesis Implantation, Humans, Male, Middle Aged, Retrospective Studies, Rifampin therapeutic use, Endocarditis, Bacterial microbiology, Gram-Positive Bacterial Infections etiology, Heart Valve Diseases surgery, Heart Valve Prosthesis adverse effects, Propionibacterium acnes, Prosthesis-Related Infections microbiology
- Abstract
Objectives: To study the characteristics of patients with Propionibacterium acnes prosthetic valve endocarditis (PVE) who required surgery., Methods: A single-centre retrospective cohort study was conducted during a 7-year period. Patients with definite infective P. acnes endocarditis, according to the modified Duke criteria, were included. An extended culture protocol was applied. Information on medical health status, surgery, antibiotic treatment and mortality was obtained., Results: Thirteen patients fulfilled the criteria for P. acnes endocarditis (0.53% of 2466 patients with valve replacement in a 7-year period). All patients were male and had a previous valve replacement. The health status of patients was poor at diagnosis of P. acnes PVE. Most patients (11 of 13, 85%) were admitted with signs of heart failure due to a significant paravalvular leak; 2 of 13 (15%) patients presented with septic emboli. Twelve patients needed redo surgery, whereas one could be treated with antibiotic therapy only. The time between the index surgery and presentation with P. acnes PVE varied between 5 and 135 months (median 26.5 months). Replacement and reconstruction of the dysfunctional valve and affected anatomical structures was mainly performed with a mechanical valve (n = 5, 42%) or a (bio-) Bentall prosthesis (n = 6, 50%). Antibiotic therapy consisted of penicillin with or without rifampicin for 6 weeks after surgery. The mortality in this series was low (n = 1, 8%) and no recurrent endocarditis was found during a median follow-up of 38 months., Conclusions: Propionibacterium acnes PVE is a rare complication after valve surgery. Redo surgery is often required. Treatment of the dysfunctional prosthetic aortic valve most often consists of root replacement, in combination with antibiotic therapy., (© The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)
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- 2016
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32. Leflunomide as part of the treatment for multidrug-resistant cytomegalovirus disease after lung transplantation: case report and review of the literature.
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Verkaik NJ, Hoek RA, van Bergeijk H, van Hal PT, Schipper ME, Pas SD, Beersma MF, Boucher CA, Jedema I, Falkenburg F, Hoogsteden HC, van den Blink B, and Murk JL
- Subjects
- Cytomegalovirus drug effects, Cytomegalovirus Infections transmission, Drug Resistance, Viral, Drug Therapy, Combination, Female, Foscarnet therapeutic use, Ganciclovir therapeutic use, Humans, Immunoglobulins therapeutic use, Leflunomide, Middle Aged, Viral Load, Antiviral Agents therapeutic use, Cytomegalovirus Infections drug therapy, Isoxazoles therapeutic use, Lung Transplantation adverse effects
- Abstract
Treatment of cytomegalovirus (CMV) disease in transplant patients is challenging and, with antiviral resistance to first-line drugs, it remains uncertain which treatment algorithm to follow. Some data suggest that leflunomide, a pyrimidine synthesis inhibitor, can be used to treat resistant CMV infections. We report a 57-year-old CMV immunoglobulin-G (IgG)-seronegative woman, who received a bilateral lung transplant (LuTx) from a CMV IgG-positive donor with CMV primary disease. The CMV strain was genotypically resistant to ganciclovir, foscarnet, and cidofovir. After starting leflunomide as add-on therapy to a multidrug anti-CMV regimen, viral load declined substantially in 2 months without adverse events. This experience is discussed against the background of existing literature on the use of leflunomide as an anti-CMV agent in LuTx recipients., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Published
- 2013
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33. Characterization of the humoral immune response during Staphylococcus aureus bacteremia and global gene expression by Staphylococcus aureus in human blood.
- Author
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den Reijer PM, Lemmens-den Toom N, Kant S, Snijders SV, Boelens H, Tavakol M, Verkaik NJ, van Belkum A, Verbrugh HA, and van Wamel WJ
- Subjects
- ATP-Binding Cassette Transporters blood, ATP-Binding Cassette Transporters genetics, ATP-Binding Cassette Transporters immunology, Aged, Antibodies, Bacterial immunology, Antigens, Bacterial immunology, Bacteremia immunology, Bacteremia microbiology, Bacterial Proteins genetics, Bacterial Proteins immunology, Female, Gene Expression, Gene Expression Profiling, Humans, Immunoglobulin A blood, Immunoglobulin A immunology, Immunoglobulin G blood, Immunoglobulin G immunology, Male, Middle Aged, Phylogeny, Staphylococcal Infections immunology, Staphylococcal Infections microbiology, Staphylococcus aureus classification, Staphylococcus aureus immunology, Staphylococcus aureus isolation & purification, Antibodies, Bacterial blood, Antigens, Bacterial blood, Bacteremia blood, Bacterial Proteins blood, Genome, Bacterial immunology, Immunity, Humoral, Staphylococcal Infections blood, Staphylococcus aureus genetics
- Abstract
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.
- Published
- 2013
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34. Streptococcus pneumoniae exposure is associated with human metapneumovirus seroconversion and increased susceptibility to in vitro HMPV infection.
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Verkaik NJ, Nguyen DT, de Vogel CP, Moll HA, Verbrugh HA, Jaddoe VW, Hofman A, van Wamel WJ, van den Hoogen BG, Buijs-Offerman RM, Ludlow M, de Witte L, Osterhaus AD, van Belkum A, and de Swart RL
- Subjects
- Child, Preschool, Haemophilus influenzae isolation & purification, Haemophilus influenzae pathogenicity, Humans, Infant, Metapneumovirus immunology, Moraxella catarrhalis isolation & purification, Moraxella catarrhalis pathogenicity, Nasopharynx microbiology, Paramyxoviridae Infections immunology, Paramyxoviridae Infections virology, Staphylococcus aureus isolation & purification, Staphylococcus aureus pathogenicity, Streptococcus pneumoniae isolation & purification, Antibodies, Viral blood, Carrier State, Disease Susceptibility, Metapneumovirus isolation & purification, Paramyxoviridae Infections epidemiology, Pneumococcal Infections complications, Streptococcus pneumoniae pathogenicity
- Abstract
It remains largely unknown which factors determine the clinical outcome of human metapneumovirus (HMPV) infections. The aim of the present study was to analyse whether exposure to bacterial pathogens can influence HMPV infections. From 57 children, serum samples and colonization data for Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pneumoniae were collected at 1.5, 6, 14 and 24 months of age. Seroconversion rates to HMPV were determined and related to bacterial carriage. Frequent nasopharyngeal carriage (≥2 times in the first 2 years of life) of S. pneumoniae, but not of the other three pathogens, was associated with increased seroconversion rates of infants to HMPV at the age of 2 years (frequently vs. less exposed, 93% vs. 59%; p <0.05). Subsequently, the susceptibility of well-differentiated normal human bronchial epithelial cells (wd-NHBE) pre-incubated with bacterial pathogens to in vitro HMPV infection was evaluated. Pre-incubation of wd-NHBE with S. pneumoniae resulted in increased susceptibility to infection with HMPV-enhanced green fluorescent protein (EGFP), as determined by enumeration of EGFP-positive cells. This was not the case for cells pre-incubated with H. influenzae, M. catarrhalis on S. aureus. We conclude that exposure to S. pneumoniae can modulate HMPV infection., (© 2011 The Authors. Clinical Microbiology and Infection © 2011 European Society of Clinical Microbiology and Infectious Diseases.)
- Published
- 2011
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35. Immunotherapeutic approaches against Staphylococcus aureus.
- Author
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Verkaik NJ, van Wamel WJ, and van Belkum A
- Subjects
- Animals, Disease Models, Animal, Humans, Immunization, Immunotherapy, Staphylococcal Infections immunology, Staphylococcal Infections therapy, Staphylococcal Vaccines immunology, Staphylococcus aureus immunology
- Abstract
Staphylococcus aureus is a major cause of life-threatening infections such as bacteremia and endocarditis. Unfortunately, many strains of this bacterial species have become resistant to certain antibiotics, including methicillin and amoxicillin. These strains are known as methicillin-resistant S. aureus (MRSA). Therefore, the prophylactic and therapeutic potential of antistaphylococcal vaccines is currently being explored with priority. In animal models, (passive) immunization with (antibodies directed against) certain S. aureus surface components, staphylococcal toxins and capsular polysaccharides protects against S. aureus colonization or infection. However, immunization studies performed in humans show less promising results. So far, not a single antistaphylococcal vaccine successfully passed clinical trials. This article focuses on the results that were obtained with immunotherapeutic approaches directed against S. aureus in animal and human studies. In addition, it is discussed whether effective immunization approaches against S. aureus are feasible in humans.
- Published
- 2011
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36. Antibody responses in furunculosis patients vaccinated with autologous formalin-killed Staphylococcus aureus.
- Author
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Holtfreter S, Jursa-Kulesza J, Masiuk H, Verkaik NJ, de Vogel C, Kolata J, Nowosiad M, Steil L, van Wamel W, van Belkum A, Völker U, Giedrys-Kalemba S, and Bröker BM
- Subjects
- Adult, Autovaccines administration & dosage, Electrophoresis, Gel, Two-Dimensional, Female, Formaldehyde, Humans, Immunoblotting, Immunoglobulin G blood, Male, Middle Aged, Prospective Studies, Serum chemistry, Staphylococcal Infections microbiology, Staphylococcal Vaccines administration & dosage, Staphylococcus aureus isolation & purification, Vaccines, Inactivated administration & dosage, Vaccines, Inactivated immunology, Young Adult, Antibodies, Bacterial blood, Autovaccines immunology, Furunculosis immunology, Furunculosis microbiology, Staphylococcal Infections immunology, Staphylococcal Vaccines immunology, Staphylococcus aureus immunology
- Abstract
Autologous vaccines (short: autovaccines) have been used since the beginning of the 20th century to treat chronic staphylococcal infections, but their mechanisms of action are still obscure. This prospective pilot study involved four patients with furunculosis who were vaccinated with autologous formalin-killed Staphylococcus aureus cells. Vaccines were individually prepared from the infecting S. aureus strain and repeatedly injected subcutaneously in increasing doses over several months. We characterized the virulence gene repertoire and spa genotype of the infecting and colonising S. aureus strains. Serum antibody responses to secreted and surface-bound bacterial antigens were determined by two-dimensional immunoblotting and flow-cytometry based assays (Luminex). All patients reported clinical improvement. Molecular characterization showed that all strains isolated from one patient over time belonged to the same S. aureus clone. Already before treatment, there was robust antibody binding to a broad range of staphylococcal antigens. Autovaccination moderately boosted the IgG response to extracellular antigens in two patients, while the antibody response of the other two patients was not affected. Similarly, vaccination moderately enhanced the antibody response against some staphylococcal surface proteins, e.g. ClfA, ClfB, SdrD and SdrE. In summary, autovaccination only slightly boosted the pre-existing serum antibody response, predominantly to bacterial surface antigens.
- Published
- 2011
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37. Development of a multiplexed bead-based immunoassay for the simultaneous detection of antibodies to 17 pneumococcal proteins.
- Author
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Shoma S, Verkaik NJ, de Vogel CP, Hermans PW, van Selm S, Mitchell TJ, van Roosmalen M, Hossain S, Rahman M, Endtz HP, van Wamel WJ, and van Belkum A
- Subjects
- Bacterial Proteins genetics, Child, Child, Preschool, Flow Cytometry, Humans, Immunoassay methods, Immunoglobulin A blood, Immunoglobulin G blood, Meningitis, Pneumococcal immunology, Meningitis, Pneumococcal microbiology, Pneumococcal Infections microbiology, Polysaccharides, Bacterial genetics, Polysaccharides, Bacterial immunology, Reproducibility of Results, Antibodies, Bacterial blood, Bacterial Proteins immunology, Pneumococcal Infections immunology, Streptococcus pneumoniae immunology
- Abstract
Presently, several pneumococcal proteins are being evaluated as potential vaccine candidates. Here, we gather novel insights in the immunogenicity of PLY, PsaA, PspA, PspC, NanA, Hyl, PpmA, SlrA, Eno, IgA1-protease, PdBD, BVH-3, SP1003, SP1633, SP1651, SP0189 and SP0376. We developed a multiplex bead-based immunoassay (xMAP(®) Technology, Luminex Corporation) to simultaneously quantify antibodies against these 17 pneumococcal proteins in serum. The median fluorescence intensity (MFI) values obtained for human pooled serum with the multiplex assay were between 82% and 111% (median 94%) of those obtained with the singleplex assays. For IgG, the coefficient of variation (CV) in serum ranged from 2% to 9%, for IgA, the CV ranged from 3% to 14% and for IgM, the CV ranged from 11% to 15%. Using this immunoassay, we showed that anti-pneumococcal antibody levels exhibited extensive inter-individual variability in young children suffering from invasive pneumococcal disease. All proteins, including the proteins with, as yet, unknown function, were immunogenic. In conclusion, the multiplex Streptococcus pneumoniae immunoassay based on proteins is reproducible. This assay can be used to monitor anti-S. pneumoniae antibody responses in a material- and time-saving manner.
- Published
- 2011
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38. Natural antibodies against several pneumococcal virulence proteins in children during the pre-pneumococcal-vaccine era: the generation R study.
- Author
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Lebon A, Verkaik NJ, Labout JA, de Vogel CP, Hooijkaas H, Verbrugh HA, van Wamel WJ, Jaddoe VW, Hofman A, Hermans PW, Ma J, Mitchell TJ, Moll HA, and van Belkum A
- Subjects
- Antibodies, Bacterial blood, Antigens, Bacterial immunology, Cell Separation, Child, Preschool, Female, Fetal Blood immunology, Flow Cytometry, Humans, Infant, Male, Pneumococcal Infections epidemiology, Pneumococcal Vaccines immunology, Respiratory Tract Infections epidemiology, Respiratory Tract Infections immunology, Respiratory Tract Infections microbiology, Streptococcus pneumoniae immunology, Antibodies, Bacterial immunology, Pneumococcal Infections immunology, Virulence Factors immunology
- Abstract
The currently available pneumococcal vaccines do not protect against all serotypes of Streptococcus pneumoniae. A shift toward nonvaccine serotypes causing colonization and invasive disease has occurred, and studies on protein-based vaccines have been undertaken. We assessed the association between specific antibodies against pneumococcal virulence proteins and colonization and respiratory tract infections (RTIs). Additionally, we assessed the extent to which colonization induces a humoral immune response. Nasopharyngeal swabs collected from children at 1.5, 6, 14, and 24 months of age were cultured for pneumococcus. Serum samples were obtained at birth and at 6, 14, and 24 months (n = 57 children providing 177 serum samples). Data were collected prior to the pneumococcal vaccine era. IgG, IgA, and IgM levels against 17 pneumococcal protein vaccine candidates were measured using a bead-based flow cytometry technique (xMAP; Luminex Corporation). Information regarding RTIs was questionnaire derived. Levels of IgG against all proteins were high in cord blood, decreased in the first 6 months and increased again thereafter, in contrast to the course of IgA and IgM levels. Specific antibodies were induced upon colonization. Increased levels of IgG against BVH-3, NanA, and SP1003 at 6 months, NanA, PpmA, PsaA, SlrA, SP0189, and SP1003 at 14 months, and SlrA at 24 months were associated with a decreased number of RTIs in the third year of life but not with colonization. Maternal antipneumococcal antibodies did not protect against pneumococcal colonization and infection. Certain antibodies against pneumococcal virulence proteins, some of which are induced by colonization, are associated with a decreased number of RTIs in children. This should be taken into account in future pneumococcal vaccine studies.
- Published
- 2011
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39. Immune evasion cluster-positive bacteriophages are highly prevalent among human Staphylococcus aureus strains, but they are not essential in the first stages of nasal colonization.
- Author
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Verkaik NJ, Benard M, Boelens HA, de Vogel CP, Nouwen JL, Verbrugh HA, Melles DC, van Belkum A, and van Wamel WJ
- Subjects
- Adult, Animals, Bacterial Proteins genetics, Bacterial Toxins metabolism, Colony Count, Microbial, Enterotoxins genetics, Female, Hemolysin Proteins metabolism, Humans, Male, Metalloendopeptidases genetics, Middle Aged, Multigene Family, Pets, Sphingomyelin Phosphodiesterase metabolism, Staphylococcus aureus genetics, Staphylococcus aureus isolation & purification, Young Adult, Genes, Viral, Immune Evasion genetics, Nasal Mucosa microbiology, Staphylococcal Infections virology, Staphylococcus Phages genetics, Staphylococcus aureus virology
- Abstract
The Staphylococcus aureus immune evasion cluster (IEC), located on β-haemolysin-converting bacteriophages (βC-Φs), encodes the immune-modulating proteins chemotaxis inhibitory protein, staphylococcal complement inhibitor (SCIN), staphylococcal enterotoxin A and staphylokinase. Its precise role in S. aureus colonization is unclear. We studied the presence of the IEC-carrying bacteriophages in human and animal S. aureus isolates, using PCR for the gene encoding SCIN (scn). Human isolates were obtained by collecting serial nasal swabs from 21 persistent carriers. S. aureus strains from 19 (90%) persistent carriers contained an IEC that was present and indistinguishable in 95% of cases at all five sampling moments over a 3-month period. Of the 77 infectious animal strains included in the study, only 26 strains (34%) were IEC-positive. Integration of these IEC-positive strains into an amplified fragment length polymorphism genotype database showed that 24 of 53 (45%) strains were human-associated and only two of 24 (8%) were 'true' animal isolates (p < 0.001). The high prevalence and stability of IEC-carrying βC-Φs in human strains suggested a role for these βC-Φs in human nasal colonization. To test this hypothesis, 23 volunteers were colonized artificially with S. aureus strain NCTC 8325-4 with or without the IEC type B-carrying βC-Φ13. Intranasal survival was monitored for 28 days after inoculation. The strain harbouring βC-Φ13 was eliminated significantly faster (median 4 days; range 1-14 days) than the strain without βC-Φ13 (median 14 days; range 2-28 days; p 0.011). In conclusion, although IEC-carrying βC-Φs are highly prevalent among human colonizing S. aureus strains, they are not essential in the first stages of S. aureus nasal colonization., (© 2010 The Authors. Journal Compilation © 2010 European Society of Clinical Microbiology and Infectious Diseases.)
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- 2011
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40. The inverse correlation between Staphylococcus aureus and Streptococcus pneumoniae colonization in infants is not explained by differences in serum antibody levels in the Generation R Study.
- Author
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Lebon A, Verkaik NJ, de Vogel CP, Hooijkaas H, Verbrugh HA, van Wamel WJ, Jaddoe VW, Hofman A, Hermans PW, Mitchell TJ, Moll HA, and van Belkum A
- Subjects
- Carrier State microbiology, Cohort Studies, Humans, Infant, Longitudinal Studies, Nasopharynx microbiology, Netherlands epidemiology, Pneumococcal Infections immunology, Pneumococcal Infections microbiology, Prevalence, Staphylococcal Infections immunology, Staphylococcal Infections microbiology, Staphylococcus aureus immunology, Streptococcus pneumoniae immunology, Antibodies, Bacterial blood, Carrier State epidemiology, Pneumococcal Infections epidemiology, Staphylococcal Infections epidemiology, Staphylococcus aureus isolation & purification, Streptococcus pneumoniae isolation & purification
- Abstract
Colonization rates of Streptococcus pneumoniae and Staphylococcus aureus are inversely correlated in infants. Several studies have searched for determinants of this negative association. We studied the association between antipneumococcal antibodies with Staphylococcus aureus colonization and the association between antistaphylococcal antibodies with pneumococcal colonization in healthy children in the pneumococcal vaccine era. In the first year of life, no association between maternal IgG levels and colonization was seen. In addition, no association between the IgG and IgA levels in the child versus colonization status was seen.
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- 2011
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41. Induction of antibodies by Staphylococcus aureus nasal colonization in young children.
- Author
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Verkaik NJ, Lebon A, de Vogel CP, Hooijkaas H, Verbrugh HA, Jaddoe VW, Hofman A, Moll HA, van Belkum A, and van Wamel WJ
- Subjects
- Age Factors, Antigens, Bacterial immunology, Bacterial Proteins immunology, Carrier State microbiology, Child, Preschool, Complement Inactivator Proteins immunology, Flow Cytometry methods, Humans, Immunity, Maternally-Acquired, Immunoglobulin A blood, Immunoglobulin G blood, Immunoglobulin M blood, Infant, Infant, Newborn, Receptors, Cell Surface immunology, Staphylococcal Infections microbiology, Staphylococcus aureus isolation & purification, Antibodies, Bacterial blood, Carrier State immunology, Nasal Mucosa microbiology, Staphylococcal Infections immunology, Staphylococcus aureus immunology
- Abstract
In order to develop novel antistaphylococcal strategies, understanding the determinants of carriage and how humans respond to Staphylococcus aureus exposure is essential. Here, the primary S. aureus-specific humoral immune response and its association with nasal colonization was studied in young children. Sera from 57 colonized or non-colonized children, serially collected at birth and at 6, 14 and 24 months, were analysed for IgG, IgA and IgM binding to 19 staphylococcal proteins, using flow cytometry-based technology. The antibody responses showed extensive inter-individual variability. On average, the levels of antistaphylococcal IgA and IgM increased from birth until the age of 2 years (p <0.05), whereas the levels of IgG decreased (p <0.001). Placentally transferred maternal IgG did not protect against colonization. In colonized children, IgG and IgA levels for a number of proteins were higher than in non-colonized children. At both 14 and 24 months, the levels of IgG against chemotaxis inhibitory protein of S. aureus (at 24 months; median fluorescence intensity, 4928 vs. 24, p <0.05), extracellular fibrinogen-binding protein (987 vs. 604, p <0.05), and iron-responsive surface determinant H (62 vs. 5, p <0.05) were significantly higher in colonized children. The levels of IgA against CHIPS, IsdH and IsdA were higher (p <0.05). Therefore, CHIPS, Efb, IsdA and IsdH seem to play a role in nasal colonization of young children.
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- 2010
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42. Heterogeneity of the humoral immune response following Staphylococcus aureus bacteremia.
- Author
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Verkaik NJ, Boelens HA, de Vogel CP, Tavakol M, Bode LG, Verbrugh HA, van Belkum A, and van Wamel WJ
- Subjects
- Adult, Aged, Antibodies, Bacterial blood, Antibodies, Bacterial immunology, Bacteremia microbiology, Child, Preschool, Cluster Analysis, Electrophoresis, Gel, Pulsed-Field, Female, Humans, Immunity, Humoral immunology, Immunoglobulin Isotypes blood, Immunoglobulin Isotypes immunology, Infant, Newborn, Longitudinal Studies, Male, Middle Aged, Staphylococcal Infections microbiology, Staphylococcus aureus genetics, Statistics, Nonparametric, Virulence genetics, Bacteremia immunology, Staphylococcal Infections immunology, Staphylococcus aureus immunology
- Abstract
Expanding knowledge on the humoral immune response in Staphylococcus aureus-infected patients is a mandatory step in the development of vaccines and immunotherapies. Here, we present novel insights into the antibody responses following S. aureus bacteremia. Fifteen bacteremic patients were followed extensively from diagnosis onwards (median 29 days, range 9-74). S. aureus strains (median 3, range 1-6) and serial serum samples (median 16, range 6-27) were collected. Strains were genotyped by pulsed-field gel electrophoresis (PFGE) and genes encoding 19 staphylococcal proteins were detected by polymerase chain reaction (PCR). The levels of IgG, IgA, and IgM directed to these proteins were determined using bead-based flow cytometry. All strains isolated from individual patients were PFGE-identical. The genes encoding clumping factor (Clf) A, ClfB, and iron-responsive surface-determinant (Isd) A were detected in all isolates. Antigen-specific IgG levels increased more frequently than IgA or IgM levels. In individual patients, different proteins induced an immune response and the dynamics clearly differed. Anti-ClfB, anti-IsdH, and anti-fibronectin-binding protein A IgG levels increased in 7 of 13 adult patients (p < 0.05). The anti-IsdA IgG level increased in 12 patients (initial to peak level: 1.13-10.72 fold; p < 0.01). Peak level was reached 7-37 days after diagnosis. In a bacteremic 5-day-old newborn, antistaphylococcal IgG levels declined from diagnosis onwards. In conclusion, each bacteremic patient develops a unique immune response directed to different staphylococcal proteins. Therefore, vaccines should be based on multiple components. IsdA is immunogenic and, therefore, produced in nearly all bacteremic patients. This suggests that IsdA might be a useful component of a multivalent staphylococcal vaccine.
- Published
- 2010
- Full Text
- View/download PDF
43. Immunogenicity of toxins during Staphylococcus aureus infection.
- Author
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Verkaik NJ, Dauwalder O, Antri K, Boubekri I, de Vogel CP, Badiou C, Bes M, Vandenesch F, Tazir M, Hooijkaas H, Verbrugh HA, van Belkum A, Etienne J, Lina G, Ramdani-Bouguessa N, and van Wamel WJ
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Bacterial Toxins genetics, Case-Control Studies, Child, Child, Preschool, Female, Humans, Immunoglobulin G immunology, Infant, Infant, Newborn, Logistic Models, Male, Middle Aged, Prevalence, Reproducibility of Results, Staphylococcal Infections epidemiology, Staphylococcus aureus genetics, Staphylococcus aureus immunology, Statistics, Nonparametric, Antibodies, Bacterial immunology, Bacterial Toxins immunology, Staphylococcal Infections microbiology, Staphylococcus aureus pathogenicity
- Abstract
Background: Toxins are important Staphylococcus aureus virulence factors, but little is known about their immunogenicity during infection. Here, additional insight is generated., Methods: Serum samples from 206 S. aureus-infected patients and 201 hospital-admitted control subjects were analyzed for immunoglobulin (Ig) G binding to 20 toxins, using flow-cytometry based technology. Antibody levels were associated with polymerase chain reaction-defined presence of toxin genes in homologous S. aureus isolates., Results: IgG levels directed to exfoliative toxin (ET) A, ETB, gamma hemolysin B (HlgB), leukocidin (Luk) D, LukE, LukS, staphylococcal enterotoxin (SE) A, SEE, SEH, SEI, and SElM were higher in S. aureus-infected patients than in control subjects (P < .05). Furthermore, in the S. aureus-infected patient group, IgG levels were higher if genes encoding ETA, ETB, SEA, SEC, SEH, SElQ, toxic shock syndrome toxin-1 (TSST-1), or Panton-Valentine leukocidin (PVL) were present in the infectious isolate (P< .05). Levels of anti-SEA IgG increased during infections with sea-positive (median fluorescence intensity from 11,555 to 12,388; P<.05) but not sea-negative strains. In addition, anti-LukS IgG levels increased during skin and soft-tissue infections with luk-PV-positive (median fluorescence intensity from 15,231 to 15,911; P<.05) but not luk-PV-negative strains. Bacteremia was associated with sea (odds ratio, 3.4; 95% confidence interval, 1.2-10.0) and tst (odds ratio, 5.7; 95% confidence interval, 1.6-20.8). Skin and soft-tissue infections and bone and joint infections were associated with luk-PV (odds ratio, 2.5; 95% confidence interval, 1.2-5.2)., Conclusions: Many toxins are expressed in vivo and recognized by the immune system during staphylococcal infections, suggesting their involvement in S. aureus pathogenesis.
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- 2010
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44. Induction of Staphylococcus aureus-specific IgA and agglutination potency in milk of cows by mucosal immunization.
- Author
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Tempelmans Plat-Sinnige MJ, Verkaik NJ, van Wamel WJ, de Groot N, Acton DS, and van Belkum A
- Subjects
- Aged, Agglutination, Animals, Cattle, Child, Humans, Staphylococcal Infections microbiology, Staphylococcus aureus isolation & purification, Antibodies, Bacterial immunology, Immunoglobulin A, Secretory immunology, Milk immunology, Staphylococcal Vaccines immunology, Staphylococcus aureus immunology
- Abstract
Lactating cows were immunized with inactivated Staphylococcus aureus strains and concentrated culture supernatants. Application of a repeated mucosal immunization scheme resulted in significant levels of S. aureus-specific IgA in milk of dairy cows. Average IgA titers against whole cell S. aureus increased during the first 10 weeks of immunization after which a plateau level was reached and maintained during lactation. Immune whey agglutinated both bovine and human S. aureus strains including methicillin-resistant S. aureus (MRSA) strains and recognized extracted S. aureus proteins on Western blot. ELISAs to quantify milk IgA reactive with a number of S. aureus virulence proteins (e.g. enterotoxins, microbial surface component recognizing adhesive matrix molecules (MSCRAMMs) and immune modulating proteins) and cell wall components, demonstrated the polyclonality of the IgA. Correlations observed between agglutination and specific IgA titers for whey and for purified IgA suggested functionality of the induced antibodies. Milk from immunized cows may provide a way of producing potentially therapeutic polyclonal antibodies against S. aureus colonization and infection.
- Published
- 2009
- Full Text
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45. Reclassification of Staphylococcus aureus nasal carriage types.
- Author
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van Belkum A, Verkaik NJ, de Vogel CP, Boelens HA, Verveer J, Nouwen JL, Verbrugh HA, and Wertheim HF
- Subjects
- Adult, Anti-Bacterial Agents pharmacology, Antibodies, Bacterial blood, Carrier State drug therapy, Carrier State immunology, Carrier State microbiology, Female, Humans, Male, Middle Aged, Mupirocin pharmacology, Ointments, Staphylococcal Infections drug therapy, Staphylococcal Infections immunology, Staphylococcus aureus classification, Staphylococcus aureus immunology, Young Adult, Carrier State classification, Nasal Mucosa microbiology, Staphylococcal Infections classification, Staphylococcus aureus isolation & purification
- Abstract
Background: Persistent nasal carriers have an increased risk of Staphylococcus aureus infection, whereas intermittent carriers and noncarriers share the same low risk. This study was performed to provide additional insight into staphylococcal carriage types., Methods: Fifty-one volunteers who had been decolonized with mupirocin treatment and whose carriage state was known were colonized artificially with a mixture of S. aureus strains, and intranasal survival of S. aureus was compared between carriage groups. Antistaphylococcal antibody levels were also compared among 83 carriage-classified volunteers., Results: Persistent carriers preferentially reselected their autologous strain from the inoculum mixture (P=.02). They could be distinguished from intermittent carriers and noncarriers on the basis of the duration of postinoculation carriage (154 vs. 14 and 4 days, respectively; P=.017, by log-rank test). Cultures of swab samples from persistent carriers contained significantly more colony-forming units per sample than did cultures of swab samples from intermittent carriers and noncarriers (P=.004). Analysis of serum samples showed that levels of immunoglobulin G and immunoglobulin A to 17 S. aureus antigens were equal in intermittent carriers and noncarriers but not in persistent carriers., Conclusions: Along with the previously described low risk of infection, intermittent carriers and noncarriers share similar S. aureus nasal elimination kinetics and antistaphylococcal antibody profiles. This implies a paradigm shift; apparently, there are only 2 types of nasal carriers: persistent carriers and others. This knowledge may increase our understanding of susceptibility to S. aureus infection.
- Published
- 2009
- Full Text
- View/download PDF
46. Anti-staphylococcal humoral immune response in persistent nasal carriers and noncarriers of Staphylococcus aureus.
- Author
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Verkaik NJ, de Vogel CP, Boelens HA, Grumann D, Hoogenboezem T, Vink C, Hooijkaas H, Foster TJ, Verbrugh HA, van Belkum A, and van Wamel WJ
- Subjects
- Antibodies, Bacterial blood, Antibody Specificity, Antigens, Bacterial immunology, Bacterial Toxins immunology, Enterotoxins immunology, Humans, Immunoglobulin G biosynthesis, Immunoglobulin G blood, Neutralization Tests, Reproducibility of Results, Superantigens immunology, Antibodies, Bacterial biosynthesis, Carrier State immunology, Nose microbiology, Staphylococcal Infections immunology, Staphylococcus aureus immunology
- Abstract
Background: Persistent carriers have a higher risk of Staphylococcus aureus infections than noncarriers but a lower risk of bacteremia-related death. Here, the role played by anti-staphylococcal antibodies was studied., Methods: Serum samples from 15 persistent carriers and 19 noncarriers were analyzed for immunoglobulin (Ig) G, IgA, and IgM binding to 19 S. aureus antigens, by means of Luminex technology. Nasal secretions and serum samples obtained after 6 months were also analyzed., Results: Median serum IgG levels were significantly higher in persistent carriers than in noncarriers for toxic shock syndrome toxin (TSST)-1 (median fluorescence intensity [MFI] value, 11,554 vs. 4291; P < .001) and staphylococcal enterotoxin (SE) A (742 vs. 218; P < .05); median IgA levels were higher for TSST-1 (P < .01), SEA, and clumping factor (Clf) A and B (P < .05). The in vitro neutralizing capacity of anti-TSST-1 antibodies was correlated with the MFI value (R(2) = 0.93) and was higher in persistent carriers (90.6% vs. 70.6%; P < .05). Antibody levels were stable over time and correlated with levels in nasal secretions (for IgG, R(2) = 0.87; for IgA, R(2) = 0.77)., Conclusions: Antibodies to TSST-1 have a neutralizing capacity, and median levels of antibodies to TSST-1, SEA, ClfA, and ClfB are higher in persistent carriers than in noncarriers. These antibodies might be associated with the differences in the risk and outcome of S. aureus infections between nasal carriers and noncarriers.
- Published
- 2009
- Full Text
- View/download PDF
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