Juliëtte A. Severin

Bio: Juliëtte A. Severin is an academic researcher from Erasmus University Rotterdam. The author has contributed to research in topics: Medicine & Population. The author has an hindex of 20, co-authored 64 publications receiving 1769 citations. Previous affiliations of Juliëtte A. Severin include Erasmus University Medical Center.

Genomic analysis of diversity, population structure, virulence, and antimicrobial resistance in Klebsiella pneumoniae, an urgent threat to public health

Abstract: Klebsiella pneumoniae is now recognized as an urgent threat to human health because of the emergence of multidrug-resistant strains associated with hospital outbreaks and hypervirulent strains associated with severe community-acquired infections. K. pneumoniae is ubiquitous in the environment and can colonize and infect both plants and animals. However, little is known about the population structure of K. pneumoniae, so it is difficult to recognize or understand the emergence of clinically important clones within this highly genetically diverse species. Here we present a detailed genomic framework for K. pneumoniae based on whole-genome sequencing of more than 300 human and animal isolates spanning four continents. Our data provide genome-wide support for the splitting of K. pneumoniae into three distinct species, KpI (K. pneumoniae), KpII (K. quasipneumoniae), and KpIII (K. variicola). Further, for K. pneumoniae (KpI), the entity most frequently associated with human infection, we show the existence of >150 deeply branching lineages including numerous multidrug-resistant or hypervirulent clones. We show K. pneumoniae has a large accessory genome approaching 30,000 protein-coding genes, including a number of virulence functions that are significantly associated with invasive community-acquired disease in humans. In our dataset, antimicrobial resistance genes were common among human carriage isolates and hospital-acquired infections, which generally lacked the genes associated with invasive disease. The convergence of virulence and resistance genes potentially could lead to the emergence of untreatable invasive K. pneumoniae infections; our data provide the whole-genome framework against which to track the emergence of such threats.

Withdrawal of a novel-design duodenoscope ends outbreak of a VIM-2-producing Pseudomonas aeruginosa

Abstract: Background and study aims: Infections are a recognized risk of endoscopic retrograde cholangiopancreatography (ERCP). This paper reports on a large outbreak of VIM-2-producing Pseudomonas aeruginosa that was linked to the use of a recently introduced duodenoscope with a specific modified design (Olympus TJF-Q180V). Methods: Epidemiological investigations and molecular typing were executed in order to identify the source of the outbreak. Audits on implementation of infection control measures were performed. Additional infection control strategies were implemented to prevent further transmission. The design and the ability to clean and disinfect the duodenoscope were evaluated, and the distal tip was dismantled. Results: From January to April 2012, 30 patients with a VIM-2-positive P. aeruginosa were identified, of whom 22 had undergone an ERCP using a specific duodenoscope, the TJF-Q180V. This was a significant increase compared with the hospital-wide baseline level of 2 – 3 cases per month. Clonal relatedness of the VIM-2 P. aeruginosa was confirmed for all 22 cases and for the VIM-2 strain isolated from the recess under the forceps elevator of the duodenoscope. An investigational study of the new modified design, including the dismantling of the duodenoscope tip, revealed that the fixed distal cap hampered cleaning and disinfection, and that the O-ring might not seal the forceps elevator axis sufficiently. The high monthly number of cases decreased below the pre-existing baseline level following withdrawal of the TJF-Q180V device from clinical use. Conclusions: Duodenoscope design modifications may compromise microbiological safety as illustrated by this outbreak. Extensive pre-marketing validation of the reprocessability of any new endoscope design and stringent post-marketing surveillance are therefore mandatory.

A Systematic Review and Meta-Analyses Show that Carbapenem Use and Medical Devices Are the Leading Risk Factors for Carbapenem-Resistant Pseudomonas aeruginosa

Abstract: A systematic review and meta-analyses were performed to identify the risk factors associated with carbapenem-resistant Pseudomonas aeruginosa and to identify sources and reservoirs for the pathogen. A systematic search of PubMed and Embase databases from 1 January 1987 until 27 January 2012 identified 1,662 articles, 53 of which were included in a systematic review and 38 in a random-effects meta-analysis study. The use of carbapenem, use of fluoroquinolones, use of vancomycin, use of other antibiotics, having medical devices, intensive care unit (ICU) admission, having underlying diseases, patient characteristics, and length of hospital stay were significant risk factors in multivariate analyses. The meta-analyses showed that carbapenem use (odds ratio [OR] = 7.09; 95% confidence interval [CI] = 5.43 to 9.25) and medical devices (OR = 5.11; 95% CI = 3.55 to 7.37) generated the highest pooled estimates. Cumulative meta-analyses showed that the pooled estimate of carbapenem use was stable and that the pooled estimate of the risk factor "having medical devices" increased with time. We conclude that our results highlight the importance of antibiotic stewardship and the thoughtful use of medical devices in helping prevent outbreaks of carbapenem-resistant P. aeruginosa.

Antimicrobial resistance among commensal isolates of Escherichia coli and Staphylococcus aureus in the Indonesian population inside and outside hospitals.

Abstract: The prevalence of antimicrobial resistance among the commensal microflora was examined in the Indonesian population inside and outside hospitals. A total of 3,995 individuals were screened in two major urban centers. Among Escherichia coli from rectal samples (n = 3,284) the prevalence of resistance to ciprofloxacin and other classes of antibiotics was remarkably high, especially in individuals at the time of discharge from hospital. Staphylococcus aureus isolates (n = 361) were often resistant to tetracycline (24.9%), but this was not associated with hospital stay. Two S. aureus isolates harbored the mecA gene. Regional differences in resistance rates exist, suggesting regional differences in selection pressure, i.e., antibiotic usage patterns. The results show that antimicrobial resistance among commensal E. coli and S. aureus has emerged in Indonesia.

Molecular characterization of extended-spectrum β-lactamases in clinical Escherichia coli and Klebsiella pneumoniae isolates from Surabaya, Indonesia

Abstract: BACKGROUND: No detailed reports regarding extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae are currently available from Indonesia, the fourth most populous country in the world. METHODS: A survey was carried out to investigate the molecular epidemiology and genetic characteristics of clinical ESBL-producing Escherichia coli and Klebsiella pneumoniae isolates originating from the Dr. Soetomo Academic Hospital in Surabaya, Indonesia, over a 4 month period (January to April 2005). ESBLs were characterized by isoelectric focusing and PCR assays. Clonality of the isolates was assessed by PFGE and repetitive-sequence-based PCR (rep-PCR). Phylogenetic grouping was performed among CTX-M-15-producing E. coli. RESULTS: In total, 73 consecutive non-duplicate ESBL-positive E. coli and 72 K. pneumoniae strains were isolated. The bla(CTX-M-15) gene was found to be highly prevalent (69/73 strains, 94.5%) among the 73 ESBL-positive E. coli isolates. The gene was detected in both clonal and non-clonal isolates, as defined by PFGE and rep-PCR. Sixteen CTX-M-15-positive E. coli could be assigned to a single rep-PCR type and phylogenetic group B2 and belonged to the well-known O25b-ST131 clone. Among the 72 ESBL-positive K. pneumoniae isolates, bla(CTX-M-15) was again the most prevalent ESBL (40/72, 55.6%). Several SHV-type enzymes were also frequently detected: SHV-5 (n = 28); SHV-12 (n = 13); and SHV-2 (n = 6). TEM-type ESBLs were not detected in any of the isolates. CONCLUSIONS: Indonesia is another developing country affected by the emergence and spread of bacterial strains harbouring ESBL genes, including the CTX-M-15-producing B2-E. coli O25b-ST131 clone.

Department of health & human services

Abstract: Vision for Transformation Strengths: The SHSIP describes a holistic transformation plan and ensures connections between various plan components. The State’s Plan seeks to reward health care providers for better care, smarter spending, and healthier people through higher quality, instead of quantity of services by utilizing valuebased purchasing across public and private payers. The SHSIP provides a well-detailed description of the proposed value-based models of care through the Patient-Centered Medical Home (PCMH) model, resulting in the statewide implementation of Accountable Health Communities (AHCs). The SHSIP outlines a long-term vision of building and expanding the PCMH model into a Community Centered Health Homes (CCHHs) model, which will focus on prevention and collaboration with other communitybased organizations. Another strength identified is the amount of existing PCMHs operating within the State. The SHSIP provides a course of action to assist non-PCMH practices to become nationally certified, as well as, goals for a single, statewide PCMH model to be used by all providers and payers within the state. The implementation of the AHCs will be key in addressing social determinants of health within various communities and seems to align well with the PCMH goals. This focus on population and community health will enable the State to make a broader impact and support the long-term goal of moving towards a CCHH model. The focus on the improvement of clinical, behavioral, and oral health care within the urban, rural, and frontier communities is well aligned and consistent with the SIM goals and the overall Triple Aim initiative. Figure 18: Driver Diagram clearly shows how the State plans to achieve the Triple Aim by 2020.

Nasal Carriage as a Source of Staphylococcus aureus Bacteremia

Abstract: of antibiotics, whether there was an explicit note in the medical chart in which the physician diagnosed a true bacteremia, and the Centers for Disease Control surveillance criteria for primary bloodstream infection. Agreement between same-strain bacteremia and each definition was examined, based on the assumption that most true infections should be the result of a single strain. The study sample consisted of 42 patients and 106 isolates. Nineteen of the 42 bacteremias (45%) were the same strain. Classification of bacteremias as same-strain correlated poorly with all three clinical assessments (range of percentage agreement, 50%-57%; range of kappa statistic, 0.01-0.15). There were both false-positive and false-negative errors. Patients with three or more positive blood cultures were more likely to have same-strain bacteremia than those with only two positive cultures (11/15 [73%] vs 8/27 [30%], P=.006). Pulsed-field gel electrophoresis was more discriminating than AP PCR (percentage agreement, 83%; kappa, 0.67). The authors concluded that molecular typing correlated poorly with clinical criteria for true bacteremia, suggesting either that true bacteremias are frequently the result of multiple strains or that the commonly used clinical criteria are not accurate for distinguishing contamination from true bacteremia. Vancomycin treatment of clinically defined coagulase-negative staphylococcal bacteremia may frequently be unnecessary. FROM: Seo SK, Venkataraman L, DeGirolami PC, Samore MH. Molecular typing of coagulase-negative staphylococci from blood cultures does not correlate with clinical criteria for true bacteremia. Am J Med 2000;109:697-704.

Global Epidemiology of Campylobacter Infection

Abstract: Campylobacter jejuni infection is one of the most widespread infectious diseases of the last century. The incidence and prevalence of campylobacteriosis have increased in both developed and developing countries over the last 10 years. The dramatic increase in North America, Europe, and Australia is alarming, and data from parts of Africa, Asia, and the Middle East indicate that campylobacteriosis is endemic in these areas, especially in children. In addition to C. jejuni, there is increasing recognition of the clinical importance of emerging Campylobacter species, including Campylobacter concisus and Campylobacter ureolyticus. Poultry is a major reservoir and source of transmission of campylobacteriosis to humans. Other risk factors include consumption of animal products and water, contact with animals, and international travel. Strategic implementation of multifaceted biocontrol measures to reduce the transmission of this group of pathogens is paramount for public health. Overall, campylobacteriosis is still one of the most important infectious diseases that is likely to challenge global health in the years to come. This review provides a comprehensive overview of the global epidemiology, transmission, and clinical relevance of Campylobacter infection.

A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

Abstract: Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions. Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other regions so efforts at reducing antibiotic consumption may need to be strengthened in this area. Increased consumption of antibiotics may not only produce greater resistance at the individual patient level but may also produce greater resistance at the community, country, and regional levels, which can harm individual patients.

Escherichia coli O25b-ST131: a pandemic, multiresistant, community-associated strain

Abstract: Escherichia coli sequence type 131 (ST131) is a worldwide pandemic clone, causing predominantly community-onset antimicrobial-resistant infection. Its pandemic spread was identified in 2008 by utilizing multilocus sequence typing (MLST) of CTX-M-15 extended-spectrum β-lactamase-producing E. coli from three continents. Subsequent research has confirmed the worldwide prevalence of ST131 harbouring a broad range of virulence and resistance genes on a transferable plasmid. A high prevalence of the clone (∼30%-60%) has been identified amongst fluoroquinolone-resistant E. coli. In addition, it potentially harbours a variety of β-lactamase genes; most often, these include CTX-M family β-lactamases, and, less frequently, TEM, SHV and CMY β-lactamases. Our knowledge of ST131's geographical distribution is incomplete. A broad distribution has been demonstrated amongst antimicrobial-resistant E. coli from human infection in Europe (particularly the UK), North America, Canada, Japan and Korea. High rates are suggested from limited data in Asia, the Middle East and Africa. The clone has also been detected in companion animals, non-companion animals and foods. The clinical spectrum of disease described is similar to that for other E. coli, with urinary tract infection predominant. This can range from cystitis to life-threatening sepsis. Infection occurs in humans of all ages. Therapy must be tailored to the antimicrobial resistance phenotype of the infecting isolate and the site of infection. Phenotypic detection of the ST131 clone is not possible and DNA-based techniques, including MLST and PCR, are described.